Effects of quercetin on exercise performance, physical activity and blood supply in a novel model of sustained hind-limb ischaemia

Background: There are currently few effective drugs to treat the leg symptoms of peripheral arterial disease (PAD). Previous studies have suggested that the nutraceutical, quercetin, can improve exercise performance and reduce pain sensitivity in healthy mice and improve blood supply in a rodent model of acute hind-limb ischaemia. These models may not be relevant to people with PAD. The aim of this study was to examine the effect of quercetin on exercise performance, physical activity and blood supply in a novel mouse model of sustained hind-limb ischaemia. Methods: Hind-limb ischaemia was induced in 6-month-old male apolipoprotein E-deficient mice using a novel two-stage surgical procedure. Five days after induction of ischaemia, mice were allocated to commence dietary quercetin or a control diet for 4 weeks. The primary outcome was exercise performance evaluated using a treadmill test. Other outcomes included physical activity, estimated by an open field test, and hind-limb blood supply, assessed by laser Doppler monitoring. Results: A sustained reduction in relative limb blood supply (P < 0.001) was achieved consistently in all 48 mice before allocation to a control (n = 24) or quercetin (n = 24) diet. Quercetin did not improve exercise performance (P = 0.785), physical activity (P = 0.151) or relative limb blood supply (P = 0.954) over the 4-week assessment period. Conclusion: These data suggest that quercetin does not improve exercise performance, physical activity or limb blood supply in mice with sustained hind-limb ischaemia, and therefore is unlikely be an effective treatment for PAD

Author response to: Peak wall stress and peak wall rupture index in ruptured and asymptomatic intact abdominal aortic aneurysms

[Extract] Dear Editor. The Townsville Hospital and Health Services Study, Education and Research Trust Fund, and Queensland Government supported this work. JG holds a Practitioner Fellowship from the National Health and Medical Research Council (1117061) and a Senior Clinical Research Fellowship from the Queensland Government, Australia. JVM holds an Advance Queensland Mid-Career fellowship from the Queensland Government. TPS holds a Junior Doctor Research Fellowship from the Queensland Government. We thank Miller and Wittek for the correspondence related to our publication

Comparison of peak wall stress and peak wall rupture index in ruptured and asymptomatic intact abdominal aortic aneurysms

Background: Previous studies have suggested that finite element analysis (FEA) can estimate the rupture risk of an abdominal aortic aneurysm (AAA); however, the value of biomechanical estimates over measurement of AAA diameter alone remains unclear. This study aimed to compare peak wall stress (PWS) and peak wall rupture index (PWRI) in participants with ruptured and asymptomatic intact AAAs. Methods: The reproducibility of semiautomated methods for estimating aortic PWS and PWRI from CT images was assessed. PWS and PWRI were estimated in people with ruptured AAAs and those with asymptomatic intact AAAs matched by orthogonal diameter on a 1 : 2 basis. Spearman's correlation coefficient was used to assess the association between PWS or PWRI and AAA diameter. Independent associations between PWS or PWRI and AAA rupture were identified by means of logistic regression analyses. Results: Twenty individuals were included in the analysis of reproducibility. The main analysis included 50 patients with an intact AAA and 25 with a ruptured AAA. Median orthogonal diameter was similar in ruptured and intact AAAs (82·3 (i.q.r. 73·5–92·0) versus 81·0 (73·2–92·4) mm respectively; P = 0·906). Median PWS values were 286·8 (220·2–329·6) and 245·8 (215·2–302·3) kPa respectively (P = 0·192). There was no significant difference in PWRI between the two groups (P = 0·982). PWS and PWRI correlated positively with orthogonal diameter (both P < 0·001). Participants with high PWS, but not PWRI, were more likely to have a ruptured AAA after adjusting for potential confounders (odds ratio 5·84, 95 per cent c.i. 1·22 to 27·95; P = 0·027). This association was not maintained in all sensitivity analyses. Conclusion: High aortic PWS had an inconsistent association with greater odds of aneurysm rupture in patients with a large AAA

Response to letter about ‘Lack of an effective drug for abdominal aortic aneurysm’

[Extract] Dear Sir, We thank Yu and colleagues for their letter 1 about our recent review 2. We agree there was substantial heterogeneity in the design of the past abdominal aortic aneurysm (AAA) drug trials, particularly those testing antibiotics. Whilst Yu et al. have focused on I2, it should be noted that this describes the dispersion of effect sizes and does not completely describe the heterogeneity between studies. The included antibiotic trials had many methodological variations, such as different sample sizes, durations of antibiotic administration and follow‐up protocols, as outlined in Tables 1 and 2 of our review 2

Reported amount of salt added to food is associated with increased all-cause and cancer-related mortality in older men in a prospective cohort study

Background: The effect of dietary salt intake on important population outcomes such as mortality is controversial. The aim of this study was to examine the association between the dietary habit of adding salt to food and mortality in older men.\ud \ud Design, participants, setting and measurements: A risk factor questionnaire which contained a question about the dietary habit of adding salt to food was completed by 11742 community recruited older men between 1996 and 1999. The men were followed by means of the Western Australia Data Linkage System until November 30th 2010. Deaths due to cardiovascular diseases and cancers were identified using ICD-10 codes in the ranges I00–I99 and C00-D48, respectively. The association between the frequencies of adding salt to food and mortality was assessed using Kaplan Meier estimates and Cox proportional hazard analysis.\ud \ud Results: Median follow-up for survivors was 12.5 years (inter-quartile range 8.3–13.2 years). A total of 5399 deaths occurred of which the primary cause registered was cancer and cardiovascular disease in 1962 (36.3%) and 1835 (34.0%) men, respectively. The reported frequency of adding salt to food was strongly positively associated with all-cause (p<0.001), cancer-related (p<0.001) but not cardiovascular-related (p=0.649) mortality. Men reporting adding salt to their food always had a 1.12-fold (95% CI 1.05–1.20, p<0.001) and a 1.20-fold (95% CI 1.07–1.34, p=0.001) increased risk of all-cause and cancer-related mortality, respectively, after adjusting for other risk factors. Men reporting adding salt to their food sometimes had a 1.16-fold (95% CI 1.04–1.29, p=0.007) increased risk of cancer-related mortality after adjusting for other risk factors.\ud \ud Conclusion: A history of adding salt to food is associated with increased cancer-related mortality in older men

Assessment and validation of a novel angiographic scoring system for peripheral artery disease

Background: Angiography is used routinely in the assessment of lower-limb arteries, but there are few well validated angiographic scoring systems. The aim of this study was to develop and validate a novel angiographic scoring system for peripheral artery disease.\ud \ud Methods: An angiographic scoring system (the ANGIO score) was developed and applied to a sample of patients from a single vascular surgical department who underwent CT angiography of the lower limbs. The reproducibility of the ANGIO score was compared with those of the Bollinger and Trans-Atlantic inter-Society Consensus (TASC) IIb systems in a series of randomly selected patients. Associations between the ANGIO score and lower-limb ischaemia, as measured by the ankle : brachial pressure index (ABPI), and outcome events (major lower-limb amputations and cardiovascular events – myocardial infarction, stroke and cardiovascular death) were assessed.\ud \ud Results: Some 256 patients undergoing CT angiography were included. The interobserver reproducibility of the ANGIO score was better than that of the other scoring systems examined (κ = 0·90, P = 0·002). There was a negative correlation between the ANGIO score and ABPI (ρ = −0·33, P = 0·008). A higher ANGIO score was associated with an increased risk of major lower-limb amputation (hazard ratio (HR) for highest versus lowest tertile 9·30, 95 per cent c.i. 1·95 to 44·38; P = 0·005) and cardiovascular events (HR 2·73, 1·31 to 5·70; P = 0·007) following adjustment for established risk factors.\ud \ud Conclusion: The ANGIO score provided a reproducible and valid assessment of the severity of lower-limb ischaemia and risk of major amputation and cardiovascular events in these patients with peripheral artery disease

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 Vascular Surger

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 e 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 e 5.70) cm3 and 0.70 (0.19 e 1.22) mm slower than those without AOD, p ¼ .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.Evan O. Matthews, Joseph V. Moxon, Tejas P. Singh, Shivshankar Thanigaimani, Rhondda E. Jones, Thomas C. Gasser, Robert Fitridge, Jan H.N. Lindeman, Ronald L. Dalman, Jonathan Golledge, on behalf of the TEDY Investigator

Efficacy of Telmisartan to Slow Growth of Small Abdominal Aortic Aneurysms: A Randomized Clinical Trial

Key PointsQuestionDoes telmisartan reduce the growth of small abdominal aortic aneurysms? FindingsIn this placebo-controlled randomized trial of 210 participants, a significant effect of telmisartan on abdominal aortic aneurysm growth rates was not shown. Telmisartan had no effect on requirement for abdominal aortic aneurysm repair or aneurysm rupture. MeaningFurther adequately powered trials are needed to assess the efficacy of medical therapies to slow abdominal aortic aneurysm growth.ImportanceCurrently there is no drug therapy for abdominal aortic aneurysm (AAA). ObjectiveTo test the efficacy of the angiotensin receptor blocker telmisartan in slowing AAA growth in the Telmisartan in the Management of Abdominal Aortic Aneurysm (TEDY) trial. Design, Setting, and ParticipantsA randomized, double-blind, placebo-controlled trial recruited participants between September 6, 2011, and October 5, 2016, to evaluate the efficacy of telmisartan treatment in patients with AAA. Participants with 35- to 49-mm AAAs recruited from Australia, the Netherlands, and the US were randomized 1:1 to receive telmisartan, 40 mg, or identical placebo. Analyses were conducted according to intention-to-treat principles. Final follow-up was conducted on October 11, 2018, and data analysis was performed between June and November 2019. InterventionTelmisartan, 40 mg, or identical placebo. Main Outcomes and MeasuresThe primary outcome of the difference in AAA growth, assessed on core imaging laboratory-read ultrasonographic scanning, was tested with linear mixed-effects models. Other outcomes included effects on blood pressure, computed tomographic (CT)-measured AAA diameter and volume, time to AAA-related events (AAA repair or mortality due to AAA rupture), and health-related quality of life. ResultsOf 300 intended participants, 210 were enrolled and randomized to receive telmisartan (n=107) or placebo (n=103). Of patients included in the intention-to-treat analysis (telmisartan: n=106, placebo: n=101), 183 were men (88%); mean (SD) age was 73.5 (7.9) years. At 1 year, participants receiving telmisartan had mean lower systolic (8.9; 95% CI, 4.1-13.8 mm Hg; P<.001) and diastolic (7.0; 4.3-9.8 mm Hg; P<.001) blood pressure levels compared with participants receiving placebo. A total of 188 participants (91%) received at least 2 ultrasonographic scans and 133 participants (64%) had at least 2 CT scans. There was no significant difference in ultrasonographic-assessed AAA growth rates among those assigned telmisartan (1.68 mm/y) or placebo (1.78 mm/y): mean difference, -0.11 mm/y (95% CI, -0.60 to 0.38 mm/y; P=.66). Telmisartan had no significant effects on AAA growth assessed by CT-measured AAA diameter (mean difference, -0.01 mm/y; 95% CI, -0.02 to 0.01 mm/y; P=.23) or volume (mean difference, -0.02 cm(3)/y; 95% CI, -0.04 to 0.00 cm(3)/y; P=.11), AAA-related events (relative risk, 1.35; 95% CI, 0.54-3.35; P=.52), or health-related quality of life (mean difference in physical component score at 24 months, 0.4; 95% CI, 0.4-0.4; P=.80). Hypotensive symptoms (eg, syncope) were twice as common among participants receiving telmisartan compared with placebo (28 [26%] vs 13 [13%]; P=.02), but overall adverse event rates were otherwise similar for both groups. Conclusions and RelevanceThis underpowered study did not show a treatment effect for telmisartan on small AAA growth. Future trials will need to ensure adequate sample size and duration of follow-up. Trial Registrationsanzctr.org.au Identifier: ACTRN12611000931976; ClinicalTrials.gov Identifier: NCT01683084This randomized clinical trial examines the efficacy of telmisartan therapy slowing the growth of abdominal aortic aneurysm in patients with that condition.Vascular Surger

Challenges, current status and future perspectives\ud of proteomics in improving understanding,\ud diagnosis and treatment of vascular disease

Abstract Technical advances have seen the rapid adoption of genomics and multiplex\ud genetic polymorphism identification to research on vascular diseases. The utilization of proteomics\ud for the study of vascular diseases has been limited by comparison. In this review we\ud outline currently available proteomics techniques, the challenges to using these approaches\ud and modifications which may improve the utilization of proteomics in the study of vascular\ud diseases.\ud ª 2009 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved