Association of serum vitamin D with diagnosis and growth of abdominal aortic aneurysm.

Objective: We examined the associations between 25-hydroxy vitamin D (25(OH)D3) concentration and the diagnosis and growth of abdominal aortic aneurysm (AAA). Methods: AAA cases and healthy controls were recruited from vascular centers or the community. A subset of participants with AAA were monitored by repeat ultrasound examination to assess AAA growth. Serum 25(OH)D3 concentration was measured using a validated mass spectrometry method and categorized into guideline-recommended cut-points after deseasonalization. The associations between deseasonalized 25(OH)D3 concentration and AAA diagnosis and growth were examined using logistic regression and linear mixed effects modeling. Results: A total of 4673 participants consisting of 873 (455 controls and 418 cases) from Queensland and 3800 (3588 controls and 212 cases) from Western Australia were recruited. For every 1 standard deviation increase in 25(OH)D3 concentration, odds of AAA diagnosis was significantly reduced in both Queensland (adjusted odds ratio: 0.81; 95% confidence interval [CI]: 0.69-0.95; P = .009) and Western Australia (adjusted odds ratio: 0.80; 95% CI: 0.68-0.94; P = .005) cohorts. A subset of 310 eligible participants with small AAA from both regions were followed for a median of 4.2 (interquartile range: 2.0-5.8) years. Compared with vitamin D sufficient participants (50 to ˂75 nmol/L), annual mean AAA growth was significantly greater in those with higher vitamin D (≥75 nmol/L) (adjusted mean difference: 0.1 mm/y, 95% CI: 0.1-0.2; P < .001). Conclusions: High 25(OH)D3 concentration was paradoxically associated with a lower likelihood of AAA diagnosis and faster AAA growth. Further research is needed to resolve these conflicting findings.

Counseling Intervention and Cardiovascular Events in People With Peripheral Artery Disease: A Post Hoc Analysis of the BIP Randomized Clinical Trial.

Importance: It is unclear whether counseling to promote walking reduces the risk of major adverse cardiovascular events (MACE) in people with peripheral artery disease (PAD). Objective: To test whether a counseling intervention designed to increase walking reduced the risk of MACE in patients with PAD. Design, Setting, and Participants: The BIP trial was a randomized clinical trial, with recruitment performed between January 2015 and July 2018 and follow-up concluded in August 2023. Participants with walking impairment due to PAD from vascular departments in the Australian cities of Brisbane, Sydney, and Townsville were randomly allocated 1:1 to the intervention or control group. Data were originally analyzed in March 2024. Intervention: Four brief counseling sessions aimed to help patients with the challenges of increasing physical activity. Main Outcomes and Measures: The primary outcome was the between-group difference in risk of MACE, which included myocardial infarction (MI), stroke, and cardiovascular death. The relationship between Intermittent Claudication Questionnaire (ICQ) scores, PAD Quality of Life (PADQOL) scores, and MACE was examined with Cox proportional hazard regression analyses. Results: A total of 200 participants were included, with 102 allocated to the counseling intervention (51.0%) and 98 to the control group (49.0%).Participants were followed up for a mean (SD) duration of 3.5 (2.6) years. Median (IQR) participant age was 70 (63-76) years, and 56 of 200 participants (28.0%) were female. A total of 31 individuals had a MACE (composed of 19 MIs, 4 strokes, and 8 cardiovascular deaths). Participants allocated to the intervention were significantly less likely to have a MACE than participants in the control group (10 of 102 participants [9.8%] vs 21 of 98 [21.4%]; hazard ratio [HR], 0.43; 95% CI, 0.20-0.91; P = .03). Greater disease-specific quality of life (QOL) scores at 4 months (ICQ: HR per 1-percentage point increase, 0.97; 95% CI, 0.95-0.99; P < .001; PADQOL factor 3 [symptoms and limitations in physical functioning]: HR per 1-unit increase, 0.91; 95% CI, 0.84-0.98; P = .01) and at 12 months (ICQ: HR per 1-percentage point increase, 0.97; 95% CI, 0.95-0.99; P = .003; PADQOL factor 3: HR per 1-unit increase, 0.91; 95% CI, 0.84-0.98; P = .02) were associated with a lower risk of MACE. In analyses adjusted for ICQ or PADQOL factor 3 scores at either 4 or 12 months, allocation to the counseling intervention was no longer significantly associated with a lower risk of MACE. Conclusions and Relevance: This post hoc exploratory analysis of the BIP randomized clinical trial suggested that the brief counseling intervention designed to increase walking may reduce the risk of MACE, possibly due to improvement in QOL. Trial Registration: anzctr.org.au Identifier: ACTRN12614000592640.

Association of remoteness and ethnicity with major amputation following minor amputation to treat diabetes-related foot disease.

INTRODUCTION: Minor amputation is commonly needed to treat diabetes-related foot disease (DFD). Remoteness of residence is known to limit access to healthcare and has previously been associated with poor outcomes. The primary aim of this study was to examine the associations between ethnicity and remoteness of residency with the risk of major amputation and death following initial treatment of DFD by minor amputation. A secondary aim was to identify risk factors for major amputation and death following minor amputation to treat DFD. RESEARCH DESIGN AND METHODS: This was a retrospective analysis of data from patients who required a minor amputation to treat DFD between 2000 and 2019 at a regional tertiary hospital in Queensland, Australia. Baseline characteristics were collected together with remoteness of residence and ethnicity. Remoteness was classified according to the 2019 Modified Monash Model (MMM) system. Ethnicity was based on self-identification as an Aboriginal and Torres Strait Islander or non-Indigenous person. The outcomes of major amputation, repeat minor amputation and death were examined using Cox-proportional hazard analyses. RESULTS: A total of 534 participants were included, with 306 (57.3%) residing in metropolitan or regional centres, 228 (42.7%) in rural and remote communities and 144 (27.0%) were Aboriginal or Torres Strait Islander people. During a median (inter quartile range) follow-up of 4.0 (2.1-7.6) years, 103 participants (19.3%) had major amputation, 230 (43.1%) had repeat minor amputation and 250 (46.8%) died. The risks (hazard ratio [95% CI]) of major amputation and death were not significantly higher in participants residing in rural and remote areas (0.97, 0.67-1.47; and 0.98, 0.76-1.26) or in Aboriginal or Torres Strait Islander people (HR 1.44, 95% CI 0.96, 2.16 and HR 0.89, 95% CI 0.67, 1.18). Ischemic heart disease (IHD), peripheral artery disease (PAD), osteomyelitis and foot ulceration (p<0.001 in all instances) were independent risk factors for major amputation. CONCLUSION: Major amputation and death are common following minor amputation to treat DFD and people with IHD, PAD and osteomyelitis have an increased risk of major amputation. Aboriginal and Torres Strait Islander People and residents of remote areas were not at excess risk of major amputation.

Agreement of Fractional Flow Reserve Estimated by Computed Tomography With Invasively Measured Fractional Flow Reserve: A Systematic Review and Meta-Analysis.

BACKGROUND: Fractional flow reserve (FFR) is the ratio of blood pressure measured distal to a stenosis and pressure proximal to a stenosis. FFR can be estimated noninvasively using computed tomography (CT) although the usefulness of this technique remains controversial. This meta-analysis evaluated the agreement of FFR estimated by CT (FFR-CT) with invasively measured FFR. The study also evaluated the diagnostic accuracy of FFR-CT, defined as the ability of FFR-CT to classify lesions as hemodynamically significant (invasive FFR ≤0.8) or insignificant (invasive FFR >0.8). METHODS AND RESULTS: Forty-three studies reporting on 7291 blood vessels from 5236 patients were included. A moderate positive linear relationship between FFR-CT and invasively measured FFR was observed (Spearman correlation coefficient: 0.67). Agreement between the 2 measures increased as invasively measured FFR values approached 1. The overall diagnostic accuracy, sensitivity and specificity of FFR-CT were 82.2%, 80.9%, and 83.1%, respectively. Diagnostic accuracy of 90% could be demonstrated for FFR-CT values >0.90 and <0.49. The diagnostic accuracy of off-site tools was 79.4% and the diagnostic accuracy of on-site tools was 84.1%. CONCLUSIONS: The agreement between FFR-CT and invasive FFR is moderate although agreement is highest in vessels with FFR-CT >0.9. Diagnostic accuracy varies widely with FFR-CT value but is above 90% for FFR-CT values >0.90 and <0.49. Furthermore, on-site and off-site tools have similar performance. Ultimately, FFR-CT may be a useful adjunct to CT coronary angiography as a gatekeeper for invasive coronary angiogram.

A systematic review and in silico analysis of studies investigating the ischaemic penumbra proteome in animal models of experimental stroke.

Ischaemic stroke results in the formation of a cerebral infarction bordered by an ischaemic penumbra. Characterising the proteins within the ischaemic penumbra may identify neuro-protective targets and novel circulating markers to improve patient care. This review assessed data from studies using proteomic platforms to compare ischaemic penumbra tissues to controls following experimental stroke in animal models. Proteins reported to differ significantly between penumbra and control tissues were analysed in silico to identify protein-protein interactions and over-represented pathways. Sixteen studies using rat (n = 12), mouse (n = 2) or primate (n = 2) models were included. Heterogeneity in the design of the studies and definition of the penumbra were observed. Analyses showed high abundance of p53 in the penumbra within 24 hours of permanent ischaemic stroke and was implicated in driving apoptosis, cell cycle progression, and ATM- MAPK- and p53- signalling. Between 1 and 7 days after stroke there were changes in the abundance of proteins involved in the complement and coagulation pathways. Favourable recovery 1 month after stroke was associated with an increase in the abundance of proteins involved in wound healing. Poor recovery was associated with increases in prostaglandin signalling. Findings suggest that p53 may be a target for novel therapeutics for ischaemic stroke.

A case-control comparison of acute-phase peripheral blood gene expression in participants diagnosed with minor ischaemic stroke or stroke mimics.

BACKGROUND: Past studies suggest that there are changes in peripheral blood cell gene expression in response to ischaemic stroke; however, the specific changes which occur during the acute phase are poorly characterised. The current study aimed to identify peripheral blood cell genes specifically associated with the early response to ischaemic stroke using whole blood samples collected from participants diagnosed with ischaemic stroke (n = 29) or stroke mimics (n = 27) following emergency presentation to hospital. Long non-coding RNA (lncRNA), mRNA and micro-RNA (miRNA) abundance was measured by RNA-seq, and the consensusDE package was used to identify genes which were differentially expressed between groups. A sensitivity analysis excluding two participants with metastatic disease was also conducted. RESULTS: The mean time from symptom onset to blood collection was 2.6 h. Most strokes were mild (median NIH stroke scale score 2.0). Ten mRNAs (all down-regulated in samples provided by patients experiencing ischaemic stroke) and 30 miRNAs (14 over-expressed and 16 under-expressed in participants with ischaemic stroke) were significantly different between groups in the whole cohort and sensitivity analyses. No significant over-representation of gene ontology categories by the differentially expressed genes was observed. Random forest analysis suggested a panel of differentially expressed genes (ADGRG7 and miRNAs 96, 532, 6766, 6798 and 6804) as potential ischaemic stroke biomarkers, although modelling analyses demonstrated that these genes had poor diagnostic performance. CONCLUSIONS: This study provides evidence suggesting that the early response to minor ischaemic stroke is predominantly reflected by changes in the expression of miRNAs in peripheral blood cells. Further work in independent cohorts particularly in patients with more severe stroke is needed to validate these findings and investigate their clinical relevance.

Cohort Study Examining the Presentation, Distribution, and Outcomes of Peripheral Artery Disease in Aboriginal, Torres Strait Islander, and Non-Indigenous Australians.

OBJECTIVE: This retrospective cohort study investigated the anatomical distribution, severity, and outcome of peripheral artery disease (PAD) in Aboriginal and Torres Strait Islanders compared with non-indigenous Australians. METHODS: The distribution, severity, and outcome of PAD were assessed using a validated angiographic scoring system and review of medical records in a cohort of Aboriginal and Torres Strait Islander and non-indigenous Australians. The relationship between ethnicity and PAD severity, distribution, and outcome were examined using non-parametric statistical tests, Kaplan-Meier and Cox proportional hazard analyses. RESULTS: Seventy-three Aboriginal and Torres Strait Islanders and 242 non-indigenous Australians were included and followed for a median of 6.7 [IQR 2.7, 9.3] years. Aboriginal and Torres Strait Islander patients were more likely to present with symptoms of chronic limb threatening ischaemia (81% vs. 25%; p < .001), had greater median [IQR] angiographic scores for the symptomatic limb (7 [5, 10] vs. 4 [2, 7]) and tibial arteries (5 [2, 6] vs. 2 [0, 4]) and had higher risk of major amputation (HR 6.1, 95% CI 3.6 - 10.5; p < .001) and major adverse cardiovascular events (HR 1.5, 95% CI 1.0 - 2.3; p = .036) but not for revascularisation (HR 0.8, 95% CI 0.5 - 1.3; p = .37) compared with non-indigenous Australians. The associations with major amputation and major adverse cardiovascular events were no longer statistically significant when adjusted for limb angiographic score. CONCLUSION: Compared with non-indigenous patients, Aboriginal and Torres Strait Islander Australians had more severe tibial artery disease and a higher risk of major amputation and major adverse cardiovascular events.

Risk Factors for Hospital Re-admission for Diabetes Related Foot Disease: A Prospective Cohort Study.

OBJECTIVE: Diabetes related foot disease (DFD) is a common reason for admission to hospital, but the predictive factors for repeat admission are poorly defined. The primary aim of this study was to identify rates and predictive factors for DFD related hospital re-admission. METHODS: Patients admitted to hospital for treatment of DFD at a single regional centre were recruited prospectively between January 2020 and December 2020. Participants were followed for 12 months to evaluate the primary outcome of hospital re-admission. The relationship between predictive factors and re-admission were examined using non-parametric statistical tests and Cox proportional hazard analyses. RESULTS: The median age of the 190 participants was 64.9 (standard deviation 13.3) years and 68.4% were male. Forty-one participants (21.6%) identified themselves as Aboriginal or Torres Strait Islander people. One hundred participants (52.6%) were re-admitted to hospital at least once over 12 months. The commonest reason for re-admission was for treatment of foot infection (84.0% of first re-admission). Absent pedal pulses (unadjusted hazard ratio [HR] 1.90; 95% confidence interval [CI] 1.26 - 2.85), loss of protective sensation (LOPS) (unadjusted HR 1.98; 95% CI 1.08 - 3.62), and male sex (unadjusted HR 1.62; 95% CI 1.03 - 2.54) increased the risk of re-admission. After risk adjustment, only absence of pedal pulses (HR 1.92, 95% CI 1.27 - 2.91) and LOPS (HR 2.02, 95% CI 1.09 - 3.74) significantly increased the risk of re-admission. CONCLUSION: Over 50% of patients admitted to hospital for treatment of DFD are re-admitted within one year. Patients with absent pedal pulses and those with LOPS are twice as likely to be re-admitted.

Cerebrovascular Disorders.

Cerebrovascular disorders pose a global health concern. Advances in basic and clinical research, including induced pluripotent stem cell models and multi-omic approaches, have improved our understanding and management of these disorders. However, gaps in our knowledge remain. BMC Cardiovascular Disorders invites authors to submit articles investigating what drives and affects Cerebrovascular disorders to improve patient care.

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 < 0.001) were associated with significantly higher risks of AAA events. In the CART analysis, PWRI was identified as the best single predictor of AAA events at a cut-off value of > 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.

Effect of Brief Counseling by Allied Health Professionals on Step Count of People With Peripheral Artery Disease: A Randomized Clinical Trial.

Importance: It is unclear how to effectively promote walking in people with peripheral artery disease (PAD). Objective: To test whether brief counseling delivered by allied health professionals increases step count in participants with PAD. Design, Setting, and Participants: In this randomized clinical trial, participants with symptomatic PAD were recruited from sites in Australia and randomly allocated 1:1 to the counseling intervention or an attention control. Data were collected from January 2015 to July 2021, and data were analyzed from March to November 2022. Interventions: Two 1-hour face-to-face and two 15-minute telephone counseling sessions designed to increase walking. Main Outcomes and Measures: The primary outcome was the between-group difference in change in daily step count estimated by accelerometer recordings over 7 days at baseline and 4 months, using imputation for missing values. Other outcomes at 4, 12, and 24 months included step count, 6-minute walk distance, and disease-specific and generic measures of health-related quality of life. Risk of major adverse limb events was assessed over 24 months. Results: Of 200 included participants, 144 (72.0%) were male, and the mean (SD) age was 69.2 (9.3) years. The planned sample of 200 participants was allocated to the counseling intervention group (n = 102) or attention control group (n = 98). Overall, 198 (99.0%), 175 (87.5%), 160 (80.0%) and 143 (71.5%) had step count assessed at entry and 4, 12, and 24 months, respectively. There was no significant between-group difference in the primary outcome of change in daily step count over 4 months (mean steps, 415; 95% CI, -62 to 893; P = .07). Participants in the counseling group had significantly greater improvement in the secondary outcome of disease-specific Intermittent Claudication Questionnaire score at 4 months (3.2 points; 95% CI, 0.1-6.4; P = .04) and 12 months (4.3 points; 95% CI, 0.5-8.1; P = .03) but not at 24 months (1.2 points; 95% CI, -3.1 to 5.6; P = .57). Findings were similar for mean PAD Quality of Life Questionnaire component assessing symptoms and limitations in physical functioning (4 months: 1.5 points; 95% CI, 0.3-2.8; P = .02; 12 months: 1.8 points; 95% CI, 0.3-3.3; P = .02; 24 months: 1.3 points; 95% CI. -0.5 to 3.1; P = .16). There was no significant effect of the intervention on change in mean 6-minute walking distance (4 months: 9.3 m; 95% CI, -3.7 to 22.3; P = .16; 12 months: 13.8 m; 95% CI, -4.2 to 31.7; P = .13; 24 months: 1.2 m; 95% CI, -20.0 to 22.5; P = .91). The counseling intervention did not affect the rate of major adverse limb events over 24 months (12 [6.0%] in the intervention group vs 11 [5.5%] in the control group; P > .99). Conclusions and Relevance: This randomized clinical trial found no significant effect of brief counseling on step count in people with PAD. Alternate interventions are needed to enable walking. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12614000592640.

Repeatability, Completion Time, and Predictive Ability of Four Diabetes-Related Foot Ulcer Classification Systems.

INTRODUCTION: The inter and intra-observer reproducibility of measuring the Wound Ischemia foot Infection (WIfI) score is unknown. The aims of this study were to compare the reproducibility, completion times and ability to predict 30-day amputation of the WIfI, University of Texas Wound Classification System (UTWCS), Site, Ischemia, Neuropathy, Bacterial Infection and Depth (SINBAD) and Wagner classifications systems using photographs of diabetes-related foot ulcers. METHODS: Three trained observers independently scored the diabetes-related foot ulcers of 45 participants on two separate occasions using photographs. The inter- and intra-observer reproducibility were calculated using Krippendorff's α. The completion times were compared with Kruskal-Wallis and Dunn's post-hoc tests. The ability of the scores to predict 30-day amputation rates were assessed using receiver operator characteristic curves and area under the curves. RESULTS: There was excellent intra-observer agreement (α >0.900) and substantial agreement between observers (α=0.788) in WIfI scoring. There was moderate, substantial, or excellent agreement within the three observers (α>0.599 in all instances except one) and fair or moderate agreement between observers (α of UTWCS=0.306, α of SINBAD=0.516, α of Wagner=0.374) for the other three classification systems. The WIfI score took significantly longer (P<.001) to complete compared to the other three scores (medians and inter quartile ranges of the WIfI, UTWCS, SINBAD, and Wagner being 1.00 [0.88-1.00], 0.75 [0.50-0.75], 0.50 [0.50-0.50], and 0.25 [0.25-0.50] minutes). None of the classifications were predictive of 30-day amputation (P>.05 in all instances). CONCLUSION: The WIfI score can be completed with substantial agreement between trained observers but was not predictive of 30-day amputation.

Serum angiopoietin-1 concentration does not distinguish patients with ischaemic stroke from those presenting to hospital with ischaemic stroke mimics.

BACKGROUND: A previous study found that circulating angiopoietin-1 (angpt-1) concentrations were significantly lower in patients who had a recent ischaemic stroke compared to healthy controls. The primary aim of this study was to assess whether serum angpt-1 could be used as a diagnostic test of ischemic stroke in patients presenting to hospital as an emergency. Exploratory analyses investigated the association of proteins functionally related to angpt-1 (angpt-2, Tie-2, matrix metalloproteinase-9 and vascular endothelial growth factors A, C and D) with ischaemic stroke diagnosis. METHODS: Patients presenting to Townsville University Hospital for emergency assessment of stroke-like symptoms were consecutively recruited and provided a blood sample. After assessment by a consultant neurologist, patients were grouped into those who did, or did not have ischaemic stroke. The potential for serum angpt-1 to diagnose ischaemic stroke was assessed using receiver operator characteristic (ROC) curves. Cross-sectional analyses appraised inter-group differences in the serum concentration of other proteins. RESULTS: One-hundred and twenty-six patients presenting to Townsville University Hospital for emergency assessment of stroke-like symptoms were recruited (median time from symptom onset to hospital presentation: 2.6 (inter-quartile range: 1.2-4.6) hours). Serum angpt-1 had poor ability to diagnose ischaemic stroke in analyses using the whole cohort, or in sensitivity analyses (area under the ROC curve 0.51 (95% CI: 0.41-0.62) and 0.52 (95% CI: 0.39-0.64), respectively). No associations of serum angpt-1 concentration with ischaemic stroke severity, symptom duration or aetiology were observed. Serum concentrations of the other assessed proteins did not differ between patient groups. CONCLUSIONS: Serum angpt-1 concentration is unlikely to be useful for emergency diagnosis of ischaemic stroke.

Colchicine Does Not Reduce Abdominal Aortic Aneurysm Growth in a Mouse Model.

Background and Aims: The nacht domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome is upregulated in human abdominal aortic aneurysm (AAA), but its pathogenic role is unclear. The aims of this study were firstly to examine whether the inflammasome was upregulated in a mouse model of AAA and secondly to test whether the inflammasome inhibitor colchicine limited AAA growth. Methods: AAA was induced in eight-week-old male C57BL6/J mice with topical application of elastase to the infrarenal aorta and oral 3-aminopropionitrile (E-BAPN). For aim one, inflammasome activation, abdominal aortic diameter, and rupture were compared between mice with AAA and sham controls. For aim two, 3 weeks after AAA induction, mice were randomly allocated to receive colchicine (n = 28, 0.2 mg/kg/d) or vehicle control (n = 29). The primary outcome was the rate of maximum aortic diameter increase measured by ultrasound over 13 weeks. Results: There was upregulation of NLRP3 markers interleukin- (IL-) 1ß (median, IQR; 15.67, 7.11-22.60 pg/mg protein versus 6.87, 4.54-11.60 pg/mg protein, p = .048) and caspase-1 (109, 83-155 relative luminosity units (RLU) versus 45, 38-65 RLU, p < .001) in AAA samples compared to controls. Aortic diameter increase over 80 days (mean difference, MD, 4.3 mm, 95% CI 3.3, 5.3, p < .001) was significantly greater in mice in which aneurysms were induced compared to sham controls. Colchicine did not significantly limit aortic diameter increase over 80 days (MD -0.1 mm, 95% CI -1.1, 0.86, p = .922). Conclusions: The inflammasome was activated in this mouse model of AAA; however, daily oral administration of colchicine did not limit AAA growth.

Effect of Telmisartan on the Peak Wall Stress and Peak Wall Rupture Index of Small Abdominal Aortic Aneurysms: An Exploratory Analysis of the TEDY Trial.

OBJECTIVE: This study was an unplanned exploratory analysis of a subset of participants from the Telmisartan in the Management of Abdominal Aortic Aneurysm (TEDY) trial. It aimed to assess the efficacy of the angiotensin 1 receptor blocker telmisartan in reducing abdominal aortic aneurysm (AAA) peak wall stress (PWS) and peak wall rupture index (PWRI) among individuals with small AAAs. METHODS: Participants with AAAs measuring 35 - 49 mm in maximum diameter were randomised to receive telmisartan 40 mg or identical placebo in the TEDY trial. Participants who had computed tomography angiography performed at entry and at least one other time point during the trial (12 or 24 months) were included in the current study. Orthogonal AAA diameter, PWS, and PWRI were measured using previously validated methods. The annual change in PWS and PWRI from baseline was compared between participants allocated telmisartan or placebo using linear mixed effects models. These models were either unadjusted or adjusted for risk factors that were different in the groups at entry (p < .100) or systolic blood pressure (SBP) at one year. RESULTS: Of the 207 participants recruited to TEDY, 124 were eligible for inclusion in this study. This study included 65 and 59 participants from the telmisartan and placebo groups, respectively. The PWS and PWRI were not significantly different in the two groups at baseline. Participants allocated telmisartan had a slower annual increase in PWS (-4.19; 95% CI -8.24, -0.14 kPa/year; p = .043) and PWRI (-0.014; 95% CI -0.026, -0.001; p = .032) compared with those allocated placebo after adjusting for risk factors. After adjustment for SBP at one year, telmisartan did not significantly reduce annual increases in PWS or PWRI. CONCLUSION: The findings of this study suggest that telmisartan limits the rate of increase in PWS and PWRI of small AAAs by reducing blood pressure.

Cohort Study Examining the Association of Optimal Blood Pressure Control at Entry With Infrarenal Abdominal Aortic Aneurysm Growth.

Background and Aim: The benefit of controlling cardiovascular risk factors in slowing the progression of small abdominal aortic aneurysm (AAA) is controversial. This study investigated the association of optimal blood pressure control at entry with the growth of small AAA. Methods and Results: A total of 1,293 patients with initial AAA diameter <50 mm were followed by a median 5 (inter-quartile range, IQR, 3-7) ultrasound scans for a median of 3.6 years (IQR 1.8, 5.3). Optimal blood pressure control was defined as blood pressure ≤140/90 mmHg at recruitment. The association of optimal blood pressure control at entry with AAA growth was assessed using linear mixed effects models adjusted for established risk factors of AAA growth and factors which were unequally distributed among the blood pressure groups. Optimal blood pressure control at entry was not significantly associated with AAA growth. In the risk factor adjusted model the mean difference in AAA growth between blood pressure groups was 0.04 mm/year (95% CI -0.20, 0.13; p = 0.65). The results were similar in sensitivity analyses excluding outliers or focused on systolic or diastolic blood pressure alone. Conclusions: This observational study suggests that optimal blood pressure control at entry is not associated with slower AAA growth.

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% female) 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.

Athero-occlusive Disease Appears to be Associated with Slower Abdominal Aortic Aneurysm Growth: An Exploratory Analysis of the TEDY Trial.

OBJECTIVE: The role of atherosclerosis in abdominal aortic aneurysm (AAA) pathogenesis is controversial. The aim of this study was to compare AAA growth in patients who did and did not have concurrent athero-occlusive disease (AOD). METHODS: Patients with an AAA measuring 35 - 49 mm in maximum diameter were recruited as part of the TElmisartan in the management of abdominal aortic aneurysm (TEDY) trial. TEDY participants who had infrarenal aortic volume and orthogonal diameter assessed by computed tomography at entry and at least one other time point during the trial (12 and/or 24 months) were included. AOD was defined by prior diagnoses of coronary heart disease, stroke, or peripheral arterial disease or an ankle brachial pressure index < 0.90. The increase in AAA volume and diameter from entry for participants who did and did not have AOD was assessed using linear mixed effects models; 131 of the 210 participants recruited to TEDY were included. RESULTS: In an unadjusted analysis, the mean (95% confidence interval) annual increases in AAA volume and diameter for participants with AOD were 3.26 (0.82 - 5.70) cm3 and 0.70 (0.19 - 1.22) mm slower than those without AOD, p = .008 and .007 respectively. The association between AOD and significantly slower AAA growth was maintained after adjusting for risk factors and medications, significantly unequally distributed between participants with and without an AOD diagnosis. CONCLUSION: In an exploratory analysis of a selective cohort from the TEDY trial, AOD was associated with slower AAA growth. Validation of these findings in other cohorts is needed.