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Objective: We examined the associations between 25-hydroxy vitamin D (25(OH)D 3 ) 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)D 3 concentration was measured using a validated mass spectrometry method and categorized into guideline-recommended cut-points after deseasonalization. The associations between deseasonalized 25(OH)D 3 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)D 3 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)D 3 concentration was paradoxically associated with a lower likelihood of AAA diagnosis and faster AAA growth. Further research is needed to resolve these conflicting findings., Competing Interests: None., (© 2024 The Author(s).)

Background: The primary aim of this study was to test which of a group of four inflammation and thrombosis biomarkers were independently predictive of major adverse cardiovascular events (MACE) in patients with small abdominal aortic aneurysm (AAA)., Methods: A total of 471 participants with a 30- to 54-mm AAA had serum C-reactive protein (CRP), fibrinogen, neutrophil-lymphocyte ratio (NLR), and homocysteine measured. The primary outcome was MACE, which was defined as the first occurrence of myocardial infarction, stroke, or cardiovascular death. The association of biomarkers with events was assessed using Kaplan-Meier and Cox proportional hazard analyses. The net improvement in risk of event categorization with addition of a biomarker to clinical risk factors alone was assessed using net reclassification index., Results: Participants were followed for a median of 2.4 years (interquartile range, 0.8-5.4 years), and 102 (21.7%) had a MACE. The incidence of MACE was 13.2% in participants with CRP >3.0 mg/L, compared with 10.1% in those with CRP ≤3.0 mg/L at 2.5 years (P = .047). After adjusting for other risk factors, higher CRP was associated with a significantly higher risk of MACE (hazard ratio, 1.19; 95% confidence interval, 1.05-1.35). None of the other biomarkers were associated with the risk of MACE. According to the net reclassification index, CRP significantly improved the risk classification of MACE compared with clinical risk factors alone., Conclusions: CRP can assist in classification of risk of MACE for patients with small AAA., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: In the present study, we examined the association of immunosuppressant drug prescriptions with the growth of small abdominal aortic aneurysms (AAAs)., Methods: Participants with an AAA measuring between 30 and 50 mm were recruited from four Australian centers. AAA growth was monitored by ultrasound. The immunosuppressant drugs included conventional disease-modifying antirheumatic drugs (eg, methotrexate, sulfasalazine, leflunomide), steroids, hydroxychloroquine, other immunosuppressant drugs (eg, cyclosporine, azacitidine), or a combination of these drugs. Linear mixed effects modeling was performed to examine the independent association of an immunosuppressant prescription with AAA growth. A subanalysis examined the association of steroids with AAA growth., Results: Of the 621 patients, 34 (5.3%) had been prescribed at least one (n = 26) or more (n = 8) immunosuppressant drug and had been followed up for a median period of 2.1 years (interquartile range, 1.1-3.5 years), with a median of three ultrasound scans (interquartile range, two to five ultrasound scans). No significant difference was found in AAA growth when stratified by a prescription of immunosuppressant drugs on either unadjusted (mean difference, 0.2 mm/y; 95% confidence interval [CI], -0.4 to 0.7; P  = .589) or risk factor-adjusted (mean difference, 0.2 mm/y; 95% CI, -0.3 to 0.7; P  = .369) analyses. The findings were similar for the unadjusted (mean difference, 0.0 mm/y; 95% CI, -0.7 to 0.7; P  = .980) and risk factor-adjusted (mean difference, 0.1 mm/y; 95% CI, -0.6 to 0.7; P = .886) subanalyses focused on steroid use., Conclusions: The results from this study suggest that AAA growth is not affected by immunosuppressant drug prescription. Studies with larger sample sizes are needed before reliable conclusions can be drawn., (Crown Copyright © 2022 Published by Elsevier Inc. on behalf of the Society for Vascular Surgery.)

Background: Peripheral artery disease (PAD) is implicated in up to 50% of diabetes-related foot ulcers (DFU) and significantly contributes to morbidity and mortality in this population. An evidence-based guideline that is relevant to the national context including consideration of the unique geographical and health care system differences between Australia and other countries, and delivery of culturally safe care to First Nations people, is urgently required to improve outcomes for patients with PAD and DFU in Australia. We aimed to identify and adapt current international guidelines for diagnosis and management of patients with PAD and DFU to develop an updated Australian guideline., Methods: Using a panel of national content experts and the National Health and Medical Research Council procedures, the 2019 International Working Group on the Diabetic Foot (IWGDF) guidelines were adapted to the Australian context. The guideline adaptation frameworks ADAPTE and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were applied to the IWGDF guideline for PAD by the expert panel. Recommendations were then adopted, adapted or excluded, and specific considerations for implementation, population subgroups, monitoring and future research in Australia were developed with accompanying clinical pathways provided to support guideline implementation., Results: Of the 17 recommendations from the IWGDF Guideline on diagnosis, prognosis and management of PAD in patients with diabetes with and without foot ulcers, 16 were adopted for the Australian guideline and one recommendation was adapted due to the original recommendation lacking feasibility in the Australian context. In Australia we recommend all people with diabetes and DFU undergo clinical assessment for PAD with accompanying bedside testing. Further vascular imaging and possible need for revascularisation should be considered for all patients with non-healing DFU irrespective of bedside results. All centres treating DFU should have expertise in, and/or rapid access to facilities necessary to diagnose and treat PAD, and should provide multidisciplinary care post-operatively, including implementation of intensive cardiovascular risk management., Conclusions: A guideline containing 17 recommendations for the diagnosis and management of PAD for Australian patients with DFU was developed with accompanying clinical pathways. As part of the adaptation of the IWGDF guideline to the Australian context, recommendations are supported by considerations for implementation, monitoring, and future research priorities, and in relation to specific subgroups including Aboriginal and Torres Strait Islander people, and geographically remote people. This manuscript has been published online in full with the authorisation of Diabetes Feet Australia and can be found on the Diabetes Feet Australia website: https://www.diabetesfeetaustralia.org/new-guidelines/ ., (© 2022. The Author(s).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Thomas Manapurathe, Moxon, Krishna, Quigley, Bourke, Bourke, Jones and Golledge.)

Objective: The aim of the present study was to examine whether severe chronic venous disease (CVD) is associated with a greater risk of major adverse cardiovascular events (MACE) compared with mild CVD., Methods: Participants with CVD were prospectively recruited from outpatient vascular departments at two hospitals in North Queensland, Australia. CVD severity was ascertained by vascular specialists using the CEAP (clinical, etiologic, anatomic, pathophysiologic) classification. MACE, defined as myocardial infarction, stroke, or cardiovascular death, were identified from the outpatient follow-up and linked medical records. Kaplan-Meier and Cox proportional hazard analyses were used to examine the association of CVD severity with the occurrence of MACE. A subanalysis was performed in which participants with CEAP C5 and C6 (severe CVD) were compared with those with CEAP C2 to C4 (mild CVD)., Results: A total of 774 participants were included and followed up for a median of 3.09 years (interquartile range, 1.09-8.14 years). The participants with C6 CVD (n = 69) had a threefold greater risk of MACE (hazard ratio, 3.03; 95% confidence interval, 1.02-9.03; P = .046) compared with those with C2 CVD (n = 326) after adjusting for other risk factors. Participants with severe CVD had an increased risk of MACE compared with those with mild CVD (adjusted hazard ratio, 2.37; 95% confidence interval, 1.12-5.04; P = .024)., Conclusions: Individuals with severe CVD have an increased risk of MACE compared with those with mild CVD, independently of traditional risk factors. Further research is required to clarify the cause of the excess risk., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Depression is associated with an increased risk of cardiovascular events but its association with abdominal aortic aneurysm (AAA) progression is unknown. This study examined if a diagnosis of depression was association with more rapid AAA growth., Methods: Patients with small AAA measuring between 30 and 50 mm were recruited from surveillance programs at 4 Australian centres. Maximum AAA diameter was measured by ultrasound imaging using a standardised and reproducible protocol to monitor AAA growth. Depression was defined from medical records of treatment for depression at recruitment. Linear mixed effects modelling was performed to examine the independent association of depression with AAA growth. A propensity matched sub-analysis was performed., Results: A total of 574 participants were included of whom 73 (12.7%) were diagnosed with depression. Participants were followed with a median of 3 (Inter-quartile range (IQR): 2, 5) ultrasound scans for a median of 2.1 (IQR: 1.1, 3.5) years. The unadjusted model suggested that annual AAA growth was non-significantly reduced (mean difference: -0.3 mm/year; 95% confidence interval (CI): -0.7, 0.2; P = 0.26) in participants with a diagnosis of depression compared to other participants. After adjustment for covariates, depression was not significantly associated with AAA growth (mean difference: -0.3 mm/year; 95% CI: -0.8, 0.2; P = 0.27). Findings were similar in the propensity matched sub-analysis. Sensitivity analyses investigating the impact of initial AAA diameter and follow up on the association of depression with AAA growth found no interaction., Conclusions: This study suggested that depression was not associated with faster AAA growth., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: The aim was to examine the presentation and outcome of patients with peripheral artery occlusive and aneurysmal disease (POAD) in relation to standard modifiable cardiovascular risk factors (SMuRFs; i.e., hypertension, diabetes, hypercholesterolaemia, and smoking)., Methods: A total of 2 129 participants with POAD were recruited from three vascular clinics in Queensland, Australia. SMuRFs were defined using established criteria. Participants were followed via outpatient appointments and linked data to record the primary outcome event of major adverse cardiovascular events (MACE). The association between SMuRFs and MACE was assessed using Cox proportional hazard analysis. Subanalyses examined the association of individual SMuRFs with MACE and assessed findings separately in participants with occlusive and aneurysmal disease., Results: At recruitment 71 (3.3%), 551 (25.9%), 977 (45.9%), 471 (22.1%), and 59 (2.8%) participants had zero, one, two, three, and four SMuRFs. During a median follow up of 2.6 (interquartile range 0.4, 6.2) years, the risk of MACE was progressively higher with the increasing numbers of SMuRFs (adjusted hazard ratio [HR] 95% confidence interval [CI] 4.09, 1.29 - 12.91; 4.28, 1.37 - 13.41; 5.82, 1.84 - 18.39; and 9.42, 2.77 - 32.08; for one, two, three, or four SMuRFs, respectively) by comparison with those who were SMuRF-less at recruitment. Participants with occlusive disease were significantly more likely to have a greater number of SMuRFs than those with aneurysmal disease. In a subanalysis, there was a significantly higher risk of MACE with three or four SMuRFs in participants presenting with either occlusive or aneurysmal disease compared with those who were SMuRF-less. Hypertension, diabetes, and smoking but not hypercholesterolaemia were independently associated with increased risk of MACE., Conclusion: Very few patients presenting with POAD had no SMuRFs. There was a progressive increase in the risk of MACE in relation to the number of SMuRFs identified at entry., (Copyright © 2021 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Aim: Immune activation is strongly implicated in atherosclerotic plaque instability, however, the effect of immunosuppressant drugs on cardiovascular events in patients with peripheral artery disease (PAD) is not known. The aim of this study was to assess whether prescription of one or more immune suppressant drugs was associated with a lower risk of major adverse cardiovascular (MACE; i.e. myocardial infarction, stroke or cardiovascular events) or limb events (MALE; i.e. major amputation or requirement for peripheral revascularization) in patients with PAD., Methods: A total of 1506 participants with intermittent claudication (n = 872) or chronic limb threatening ischemia (CLTI; n = 634) of whom 53 (3.5%) were prescribed one or more immunosuppressant drugs (prednisolone 41; methotrexate 17; leflunomide 5; hydroxychloroquine 3; azathioprine 2; tocilizumab 2; mycophenolate 1; sulfasalazine 1; adalimumab 1) were recruited from 3 Australian hospitals. Participants were followed for a median of 3.9 (inter-quartile range 1.2, 7.3) years. The association of immunosuppressant drug prescription with MACE or MALE was examined using Cox proportional hazard analyses., Results: After adjusting for other risk factors, prescription of an immunosuppressant drug was associated with a significantly greater risk of MACE (Hazard ratio, HR, 1.83, 95% confidence intervals, CI, 1.11, 3.01; P = 0.017) but not MALE (HR 1.32, 95% CI 0.90, 1.92; P = 0.153). In a sub-analysis restricted to participants with CLTI findings were similar: MACE (HR 2.44, 95% CI 1.32, 4.51; P = 0.005); MALE (HR 1.38, 95% CI 0.87, 2.19; P = 0.175); major amputation (HR 1.37, 95% CI 0.49, 3.86; P = 0.547)., Conclusions: This cohort study suggested that immunosuppressant drug therapy is associated with a greater risk of MACE amongst patients with PAD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to examine whether there were independent associations between abdominal aortic diameter, size index, and height index and the risk of major adverse events in patients referred for treatment of various types of aortic and peripheral occlusive and aneurysmal disease (APOAD)., Methods: In total, 1 752 participants with a variety of APOADs were prospectively recruited between 2002 and 2020 and had a maximum abdominal aortic diameter, aortic size index (aortic diameter relative to body surface area), and aortic height index (aortic diameter relative to height) measured by ultrasound at recruitment. Participants were followed for a median of 4.6 years (interquartile range 2.0 - 8.0 years) to record outcome events, including major adverse cardiovascular events (MACE), peripheral artery surgery, abdominal aortic aneurysm (AAA) events (rupture or repair), and all cause mortality. The association between aortic size and events was assessed using Cox proportional hazard analysis. The ability of aortic size to improve risk of events classification was assessed using the net reclassification index (NRI)., Results: After adjusting for other risk factors, larger aortic diameter was associated with an increased risk of MACE (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.05 - 1.31), requirement for peripheral artery surgery (HR 2.05, 95% CI 1.90 - 2.22), AAA events (HR 3.01, 95% CI 2.77 - 3.26), and all cause mortality (HR 1.20, 95% CI 1.08 - 1.32). Findings were similar for aortic size and aortic height indices. According to the NRI, all three aortic size measures significantly improved classification of risk of peripheral artery surgery and AAA events but not MACE. Aortic size index, but not aortic diameter or aortic height index, significantly improved the classification of all cause mortality risk., Conclusion: Larger abdominal aortic diameter, size index, and height index are all independently associated with an increased risk of major adverse events in patients with established vascular disease., Competing Interests: Conflicts of interest None., (Copyright © 2021 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Objective: The aims of this study were to assess the incidence of major vascular events (MVE) and peripheral vascular events (PVE) in people with a small asymptomatic abdominal aortic aneurysm (AAA) and model the theoretical benefits and costs of an intensified low density lipoprotein cholesterol (LDL-C) lowering programme., Methods: A total of 583 participants with AAAs measuring 30 - 54 mm were included in this study. The control of LDL-C and prescription of lipid lowering drugs were assessed by dividing participants into approximately equal tertiles depending on their year of recruitment into the study. The occurrence of MVE (myocardial infarction, stroke, cardiovascular death, and coronary or non-coronary revascularisation) and PVE (non-coronary revascularisation, AAA repair, and major amputation) were recorded prospectively, and the incidence of these events was calculated using Kaplan-Meier analysis. The relative risk reduction reported for these events in a previous randomised control trial (RCT) was then applied to these figures to model the absolute risk reduction and numbers needed to treat (NTT) that could theoretically be achieved with a mean LDL-C lowering of 1 mmol/L. The maximum allowable expense for a cost effective intensive LDL-C lowering programme was estimated using a cost utility analysis., Results: At entry, only 28.5% of participants had an LDL-C of < 1.8 mmol/L and only 18.5% were prescribed a high potency statin (atorvastatin 80 mg or rosuvastatin 40 mg). The five year incidences of MVE and PVE were 38.1% and 44.7%, respectively. It was estimated that if the mean LDL-C of the cohort had been reduced by 1 mmol/L, this could have reduced the absolute risk of MVE and PVE by 6.5% (95% CI 4.4 - 8.7; NNT 15) and 5.3% (95% CI 1.4 - 7.5; NNT 19), respectively. It was estimated that the maximum allowable expense for a cost effective LDL-C lowering programme would be between $1 239 AUD (€768) and $1 582 AUD (€981) per person per annum over a five year period., Conclusion: People with a small asymptomatic AAA are at high risk of MVE and PVE. This study provides evidence of the possible benefits and allowable expense for a cost effective intensive LDL-C lowering programme in this population., (Copyright © 2021 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Objective: The costs of open and endovascular revascularisation to treat peripheral artery disease (PAD) have not been fully established. This study examined the costs of both the index admission and any readmissions to hospital within 30 days of discharge for people having revascularisation at a single centre in Australia., Methods: This was a retrospective analysis of prospectively collected data. Eligible participants were those presenting with chronic limb ischaemia requiring revascularisation between 2002 and 2017. Generalised linear modelling was used to estimate mean (95% confidence interval [95% CI]) hospital costs for the index and readmission hospital treatments., Results: A total of 302 participants presenting with intermittent claudication (n=219; 72.5%) or chronic limb threatening ischaemia (n=83; 27.5%) treated by open (n=116; 38.4%) or endovascular (n=186; 61.6%) revascularisation were included. Forty-eight (48) (15.9%) participants were readmitted within 30 days of discharge from their index admission. The mean estimated index admission hospital cost was AUD$13,827 (95% CI, $11,935-$15,818) per person. This cost was significantly greater for open as compared to endovascular revascularisation (p<0.001). The mean estimated hospital cost was AUD$15,324 ($10,944-$19,966) per person readmitted. When comparing participants treated before and after 2010, the total hospital costs decreased, mainly due to decreased lengths of hospital stay for open procedures., Conclusions: In this study the hospital costs were less for endovascular than open revascularisation of chronic limb ischaemia. Costs decreased over time. Readmission is an important contributor to the overall costs of peripheral revascularisation., (Copyright © 2021 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background: People with diabetes and peripheral artery disease (PAD) have a high risk of major adverse cardiovascular events (MACE). Prior research suggests that medical therapies aimed to control modifiable risk factors are poorly implemented in patients with PAD., Aim: To examine the association between the control of modifiable risk factors, estimated by the novel PAD-medical score, and the incidence of MACE in people with PAD and diabetes., Methods: Participants were recruited from out-patient clinics if they had a diagnosis of both PAD and diabetes. Control of reversible risk factors was assessed by a new composite measure, the PAD-medical score. This score takes into account the control of low-density lipoprotein cholesterol, blood pressure, blood glucose, smoking and prescription of an anti-platelet. Participants were followed to record incidence of myocardial infarction, stroke and cardiovascular death (MACE). The association of PAD-medical score with MACE was assessed using Cox proportional hazard analyses adjusting for age, sex and prior history of ischemic heart disease and stroke., Results: Between 2002 and 2020, a total of 424 participants with carotid artery disease ( n = 63), aortic or peripheral aneurysm ( n = 121) or lower limb ischemia ( n = 240) were prospectively recruited, and followed for a median duration (inter-quartile range) of 2.0 (0.2-4.4) years. Only 33 (7.8%) participants had the optimal PAD-medical score of five, with 318 (75%) scoring at least three out of five. There were 89 (21.0%) participants that had at least one MACE during the follow-up period. A one-unit higher PAD-medical score was associated with lower risk of MACE (HR = 0.79, 95%CI: 0.63-0.98) after adjusting for other risk factors., Conclusion: The PAD-medical score provides a simple way to assess the control of modifiable risk factors targeted by medical management aimed to reduce the incidence of MACE., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: People with peripheral artery disease are at a high risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Randomized controlled trials suggest that intensive lowering of low-density lipoprotein cholesterol (LDL-C) with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors is an effective strategy to prevent these events. This study estimated the potential benefit and cost-effectiveness of administrating PCSK9 inhibitors to a cohort of participants with peripheral artery disease., Methods: A total of 783 participants with intermittent claudication (IC; n = 582) or chronic limb-threatening ischemia (CLTI; n = 201) were prospectively recruited from three hospitals in Australia. Serum LDL-C was measured at recruitment, and the occurrence of MACE and MALE was recorded over a median (interquartile range) follow-up of 2.2 years (0.3-5.7 years). The potential benefit of administering a PCSK9 inhibitor was estimated by calculating the absolute risk reduction and numbers needed to treat (NNT) based on relative risk reductions reported in published randomized trials. The incremental cost-effectiveness ratio per quality-adjusted life year gained was estimated., Results: Intensive LDL-C lowering was estimated to lead to an absolute risk reduction in MACE of 6.1% (95% confidence interval [CI], 2.0-9.3; NNT, 16) and MALE of 13.7% (95% CI, 4.3-21.5; NNT, 7) in people with CLTI compared with 3.2% (95% CI, 1.1-4.8; NNT, 32) and 5.3% (95% CI, 1.7-8.3; NNT, 19) in people with IC. The estimated incremental cost-effectiveness ratios over a 10-year period were $55,270 USD and $32,800 USD for participants with IC and CLTI, respectively., Conclusions: This analysis suggests that treatment with a PCSK9 inhibitor is likely to be cost-effective in people with CLTI., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To assess whether survival and clinical events following elective abdominal aortic aneurysm (AAA) repair were associated with remoteness of residence in North Queensland, Australia., Methods: This retrospective cohort study included participants undergoing elective AAA repair between February 2002 and April 2020 at two hospitals in Townsville, North Queensland, Australia. Outcomes were all-cause survival and AAA-related events, defined as requirement for repeat AAA repair or AAA-related mortality. Remoteness of participant's place of residence was assessed by the Modified Monash Model classifications and estimated distance from the participants' home to the tertiary vascular centre. Cox proportional hazard analysis examined the association of remoteness with outcome., Results: The study included 526 participants undergoing elective repair by open (n = 204) or endovascular (n = 322) surgery. Fifty-four (10.2%) participants had a place of residence at a remote or very remote location. Participants' were followed for a median of 5.2 (inter-quartile range 2.5-8.3) years, during which time there were 252 (47.9%) deaths. Survival was not associated with either measure of remoteness. Fifty (9.5%) participants had at least one AAA-related event, including 30 (5.7%) that underwent at least one repeat AAA surgery and 23 (4.4%) that had AAA-related mortality. AAA-related events were more common in participants resident in the most remote areas (adjusted hazard ratio 2.83, 95% confidence intervals 1.40, 5.70) but not associated with distance from the participants' residence to the tertiary vascular centre., Conclusions: The current study found that participants living in more remote locations were more likely to have AAA-related events but had no increased mortality following AAA surgery. The findings emphasize the need for careful follow-up after AAA surgery. Further studies are needed to examine the generalisability of the findings., Competing Interests: The authors have declared that no competing interests exist.

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., Competing Interests: No competing interests.

Background and Aims: Prior epidemiological studies have suggested that individuals with gout are at greater risk of cardiovascular events, but there have been no studies in people with peripheral artery disease (PAD). The aim of this study was to investigate the relationship between gout and major adverse cardiovascular events (MACE) and all-cause mortality in people with PAD., Methods: Participants with a range of PAD presentations, including carotid artery disease, aortic or peripheral aneurysm and lower limb PAD, were prospectively recruited from outpatient vascular departments within Australia. MACE (myocardial infarction, stroke or cardiovascular death) and all-cause mortality were identified through out-patient follow-up and linked medical records. Propensity-score matching was undertaken to generate a matched cohort of patients with and without a history of gout. Kaplan-Meier survival analysis and Cox-proportional hazard analysis were used to examine the association of gout with MACE and all-cause mortality., Results: A total of 4308 people with PAD, of whom 334 had a history of gout, were included and followed for a median (inter-quartile range) of 2.1 (0.1-5.9) years. In the unadjusted analyses, participants with gout were at increased risk of MACE (hazard ratio, HR 1.37, 95% confidence intervals, CI 1.09-1.71, p = 0.006) and all-cause mortality (HR 1.38, 95% 1.13-1.68, p = 0.002), however, the associations were lost in the adjusted analyses. In the propensity-score matched cohort, gout was not significantly associated with an increased risk for MACE or all-cause mortality., Conclusions: Gout was not independently associated with increased cardiovascular events in PAD patients., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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 α 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.

Objective: Experimental studies suggest that fenofibrate prevents abdominal aortic aneurysm (AAA) development by lowering aortic osteopontin (OPN) concentration and reducing the number of macrophages infiltrating the aortic wall. The current study examined the effects of a short course of fenofibrate on AAA pathology in people with large AAAs awaiting aortic repair., Methods: This randomised double blind parallel trial included male and female participants aged ≥ 60 years who had an asymptomatic AAA measuring ≥ 50 mm and were scheduled to undergo open AAA repair. Participants were allocated to fenofibrate (145 mg/day) or matching placebo for at least two weeks before elective AAA repair. Blood samples were collected at recruitment and immediately prior to surgery. AAA biopsies were obtained during aortic surgery. The primary outcomes were (1) AAA OPN concentration; (2) serum OPN concentration; and (3) number of AAA macrophages. Exploratory outcomes included circulating and aortic concentrations of other proteins previously associated with AAA. Outcomes assessed at a single time point were compared using logistic regression. Longitudinal outcomes were compared using linear mixed effects models., Results: Forty-three participants were randomised. After three withdrawals, 40 were followed until the time of surgery (21 allocated fenofibrate and 19 allocated placebo). As expected, serum triglycerides reduced significantly from recruitment to the time of surgery in participants allocated fenofibrate. No differences in any of the primary and exploratory outcomes were observed between groups., Conclusion: A short course of 145 mg of fenofibrate/day did not lower concentrations of OPN or aortic macrophage density in people with large AAAs., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

Background The aim of this study was to assess the relationship between serum lipoprotein (a) (Lp[a]) concentration and the requirement for peripheral artery disease (PAD) operations or incidence of major adverse cardiovascular events. Methods and Results A total of 1472 people with PAD presenting with intermittent claudication (n=355), abdominal aortic aneurysm (n=989) or critical limb ischemia (n=128) were prospectively recruited from 4 outpatient clinics in Australia. Lp(a) was measured in serum samples collected at recruitment using an immunoassay. Participants were followed for a median (interquartile range) of 2.4 (0.1-6.1) years to record requirement for any PAD operation, defined to include any open or endovascular PAD intervention (lower limb peripheral revascularization, abdominal aortic aneurysm repair, other aneurysm repair, or carotid artery revascularization). Myocardial infarctions, strokes, and deaths were also recorded. The association of Lp(a) with events was assessed using Cox proportional hazard analysis adjusting for traditional risk factors. Participants with Lp(a) ≥30 mg/dL had a greater requirement for any PAD operation (hazard ratio, 1.20, 95% CI, 1.02-1.41) and lower limb peripheral revascularization alone (hazard ratio 1.33, 95% CI, 1.06-1.66) but no increased risk of major adverse cardiovascular events or all-cause mortality. Lp(a) ≥50 mg/dL and a 40 mg/dL increase in Lp(a) were also associated with an increased risk of lower limb peripheral revascularization alone but not with other outcomes. Conclusions In participants with PAD referred for hospital management those with high Lp(a) had greater requirement for lower limb peripheral revascularization but Lp(a) was not consistently associated with other clinical events.

Background Hypertension is an important risk factor for cardiovascular events in patients with peripheral artery disease; however, optimal blood pressure targets for these patients are poorly defined. This study investigated the association between systolic blood pressure ( SBP ) and cardiovascular events in a prospectively recruited patient cohort with peripheral artery disease. Methods and Results A total of 2773 patients were included and were grouped according to SBP at recruitment (≤120 mm Hg, n=604; 121-140 mm Hg, n=1065; and >140 mm Hg, n=1104). Adjusted Cox proportional hazards analyses suggested that patients with SBP ≤120 mm Hg were at greater risk of having a major cardiovascular event (myocardial infarction, stroke, or cardiovascular death) than patients with SBP of 121-140 mm Hg (adjusted hazard ratio, 1.36; 95% CI, 1.08-1.72; P=0.009). Patients with SBP >140 mm Hg had an adjusted hazard ratio of 1.23 (95% CI, 1.00-1.51; P=0.051) of major cardiovascular events compared with patients with SBP of 121-140 mm Hg. These findings were similar in sensitivity analyses only including patients receiving antihypertensive medications or focused on patients with a minimum of 3 months of follow-up. Conclusions This cohort study suggests that patients with peripheral artery disease and SBP ≤120 mm Hg are at increased risk of major cardiovascular events. The findings suggest caution in intensive SBP lowering in this patient group.

Background There is no drug therapy for abdominal aortic aneurysm ( AAA ). FAME-2 (Fenofibrate in the Management of Abdominal Aortic Aneurysm 2) was a placebo-controlled randomized trial designed to assess whether administration of 145 mg of fenofibrate/d for 24 weeks favorably modified circulating markers of AAA. Methods and Results Patients with AAA s measuring 35 to 49 mm and no contraindication were randomized to fenofibrate or identical placebo. The primary outcome measures were the differences in serum osteopontin and kallistatin concentrations between groups. Secondary analyses compared changes in the circulating concentration of AAA -associated proteins, and AAA growth, between groups using multivariable linear mixed-effects modeling. A total of 140 patients were randomized to receive fenofibrate (n=70) or placebo (n=70). By the end of the study 3 (2.1%) patients were lost to follow-up and 18 (12.9%) patients had ceased trial medication. A total of 85% of randomized patients took ≥80% of allocated tablets and were deemed to have complied with the medication regimen. Patients' allocated fenofibrate had expected reductions in serum triglycerides and estimated glomerular filtration rate, and increases in serum homocysteine. No differences in serum osteopontin, kallistatin, or AAA growth were observed between groups. Conclusions Administering 145 mg/d of fenofibrate for 24 weeks did not significantly reduce serum concentrations of osteopontin and kallistatin concentrations, or rates of AAA growth in this trial. The findings do not support the likely benefit of fenofibrate as a treatment for patients with small AAA s. Clinical Trial Registration URL : www.anzctr.org.au . Unique identifier: ACTRN 12613001039774.

Background: Abdominal aortic aneurysm (AAA) is a slowly progressive destructive process of the main abdominal artery. Experimental studies indicate that fibrates exert beneficial effects on AAAs by mechanisms involving both serum lipid modification and favourable changes to the AAA wall., Methods/design: Fenofibrate in the management of AbdoMinal aortic anEurysm (FAME) is a multicentre, randomised, double-blind, placebo-controlled clinical trial to assess the effect of orally administered therapy with fenofibrate on key pathological markers of AAA in patients undergoing open AAA repair. A total of 42 participants scheduled for an elective open AAA repair will be randomly assigned to either 145 mg of fenofibrate per day or identical placebo for a minimum period of 2 weeks prior to surgery. Primary outcome measures will be macrophage number and osteopontin (OPN) concentration within the AAA wall as well as serum concentrations of OPN. Secondary outcome measures will include levels of matrix metalloproteinases and proinflammatory cytokines within the AAA wall, periaortic fat and intramural thrombus and circulating concentrations of AAA biomarkers., Discussion: At present, there is no recognised medical therapy to limit AAA progression. The FAME trial aims to assess the ability of fenofibrate to alter tissue markers of AAA pathology., Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12612001226897 . Registered on 20 November 2012.

Objective: This study was conducted to assess whether serum homocysteine concentration was associated with the severity of primary chronic venous disease., Design: Cross-sectional study., Methods: A total of 282 primary chronic venous disease patients were enrolled from outpatient vascular services. The severity of venous disease was graded using the Clinical Etiology Anatomy Pathophysiology classification system. The association of serum homocysteine concentration with advanced primary chronic venous disease (C4-6) was assessed using the Mann Whitney U test and logistic regression analysis., Results: Median (interquartile range) serum homocysteine concentrations were 9.10 µM (7.55-10.75) and 10.40 µM (8.85-13.10) in patients with primary chronic venous disease classified by C1-3 (n = 209) and C4-6 (n = 73) grades, respectively, p < 0.001. Serum homocysteine concentration was positively associated with clinical grade 4-6 after adjusting for other risk factors including age, diabetes, male sex, hypertension, recurrent varicose veins and stroke. Patients with serum homocysteine in the third (odds ratio, 2.76, 95% confidence interval, 1.01-7.54) and fourth (odds ratio 3.29, 95% confidence interval 1.15-9.43) quartiles were more likely to have grade C4-6 chronic venous disease than subjects with serum homocysteine in the first quartile., Conclusions: Serum homocysteine is positively associated with the severity of primary chronic venous disease and therefore could play a role in promoting chronic venous disease complications., (© The Author(s) 2015.)

Background: Pre-diabetes and untreated diabetes are common in patients with peripheral artery disease however their impact on outcome has not been evaluated. We examined the association of impaired fasting glucose, diabetes and their treatment with the presentation, mortality and requirement for intervention in peripheral artery disease patients., Methods: We prospectively recruited 1637 patients with peripheral artery disease, measured fasting glucose, recorded medications for diabetes and categorised them by diabetes status. Patients were followed for a median of 1.7 years., Results: At entry 22.7% patients were receiving treatment for type 2 diabetes by oral hypoglycaemics alone (18.1%) or insulin (4.6%). 9.2% patients had non-medicated diabetes. 28.1% of patients had impaired fasting glucose (5.6-6.9 mM). Patients with non-medicated diabetes had increased mortality and requirement for peripheral artery intervention (hazards ratio 1.62 and 1.31 respectively). Patients with diabetes prescribed insulin had increased mortality (hazard ratio 1.97). Patients with impaired fasting glucose or diabetes prescribed oral hypoglycaemics only had similar outcomes to patients with no diabetes., Conclusions: Non-medicated diabetes is common in peripheral artery disease patients and associated with poor outcomes. Impaired fasting glucose is also common but does not increase intermediate term complications. Peripheral artery disease patients with diabetes requiring insulin are at high risk of intermediate term mortality.

The purpose of this study was to examine the effects of a 6-month exercise program on submaximal walking economy in individuals with peripheral arterial disease and intermittent claudication (PAD-IC). Participants (n = 16) were randomly allocated to either a control PAD-IC group (CPAD-IC, n = 6) which received standard medical therapy, or a treatment PAD-IC group (TPAD-IC; n = 10) which took part in a supervised exercise program. During a graded treadmill test, physiological responses, including oxygen consumption, were assessed to calculate walking economy during submaximal and maximal walking performance. Differences between groups at baseline and post-intervention were analyzed via Kruskal-Wallis tests. At baseline, CPAD-IC and TPAD-IC groups demonstrated similar walking performance and physiological responses. Postintervention, TPAD-IC patients demonstrated significantly lower oxygen consumption during the graded exercise test, and greater maximal walking performance compared to CPAD-IC. These preliminary results indicate that 6 months of regular exercise improves both submaximal walking economy and maximal walking performance, without significant changes in maximal walking economy. Enhanced walking economy may contribute to physiological efficiency, which in turn may improve walking performance as demonstrated by PAD-IC patients following regular exercise programs.

Background: The aim of this study was to assess the long-term clinical outcomes in terms of vascular events in patients who showed no significant or mild carotid stenosis (<50%) and thus in whom surgical intervention was not planned. Patients were recruited through referrals to a vascular laboratory between January 2000 and June 2000. One hundred thirty-two of 316 (42%) patients referred for carotid duplex scan were identified to have mild carotid artery disease., Methods: A retrospective observational study of patients identified to have mild carotid artery stenosis from a regional vascular unit in Australia was carried out. Patients were followed up over an 8-year period. Outcomes were assessed in relation to the patients' presenting complaint and risk factor profile. Outcomes included the following: (1) combined cardiovascular events (fatal and nonfatal strokes, fatal and nonfatal myocardial infarctions, and cardiac admissions, which included arrhythmias and angina), (2) strokes (both fatal and nonfatal strokes), and (3) all-cause mortality., Results: The patient sample included 75 men and 57 women. The median age of the patients was 69.9 (interquartile range: 63.4-76.7) years. There were a total of 49 vascular events in 46 of the 132 patients, including 16 nonfatal and 2 fatal myocardial infarctions, 19 admissions for cardiac reasons other than an acute coronary syndrome, and 12 nonfatal strokes. The cardiovascular and stroke rates were 33.9% and 13.0% at 7.7 years, respectively. The incidence of strokes was highest among those who presented with a previous stroke or a transient ischemic attack., Conclusions: The long-term clinical outcomes of patients who were referred for duplex ultrasonography and found to have <50% stenosis were not benign. A significant number of vascular events were observed in this study group. Those who presented with a history of stroke or transient ischemic attack were at particular risk of another stroke., (Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to examine the effects of a 12month exercise program on lower limb movement variability in patients with peripheral arterial disease (PAD). Participants (n=21) with an appropriate history of PAD and intermittent claudication (IC) volunteered for this study and were randomly allocated to either a control group (CPAD-IC) (n=11), which received normal medical therapy and a treatment group (TPAD-IC) (n=10), which received normal medical therapy treatment and a 12month supervised exercise program. All participants underwent 2D joint angular kinematic analysis during normal walking to assess lower limb movement variability and walking speed. Between-group differences were analyzed via mixed measures ANOVA. The 12month supervised exercise program made no significant impact on the lower limb movement variability or walking speed of the TPAD-IC group as determined by either intralimb joint coordination or single joint analysis techniques. Long term supervised exercise programs do not appear to influence the lower limb movement variability of PAD-IC patients.

Background: Peripheral arterial disease is a chronic obstructive disease of the arteries of the lower limb caused by atherosclerosis. The resultant decrease in blood flow can result in symptoms of pain in the lower limb on exercise known as intermittent claudication. Exercise induced pain is experienced in the calves, thigh or buttocks restricting activities of daily living and thus reducing quality of life., Methods: This study investigated lower limb movement variability in individuals with peripheral arterial disease-intermittent claudication (n=28) compared to individuals without peripheral arterial disease-intermittent claudication (control, n=25). A further aim was to examine the efficacy of various techniques used to describe single joint movement variability. All participants underwent two-dimensional angular kinematics analysis of the lower limb during normal walking. Single joint movement variability was measured using linear (spanning set and coefficient of variation) techniques. Between group differences were examined by one-way ANOVA., Findings: The peripheral arterial disease-intermittent claudication participants displayed significantly higher levels of lower limb movement variability in all joints when assessed using the coefficient of variation technique. There were no significant between group differences using the spanning set technique., Interpretation: Individuals with peripheral arterial disease-intermittent claudication have higher levels of lower limb movement variability and reduced walking speed compared to healthy age and mass matched controls. This variability may be an adaptation to the gradual onset of ischaemic pain in this population.

Background: Increased variability has been traditionally associated with decreased movement performance due to disease and aging. However, recent research indicates that variability may be of functional importance in motor control. Thus the purpose of this study was to determine whether individuals with peripheral arterial disease and suffering from intermittent claudication have reduced intralimb joint coordination variability compared to individuals without peripheral arterial disease. A further aim was to examine the efficacy of various techniques used to describe intralimb joint coordination variability., Methods: Participants with peripheral arterial disease and suffering from intermittent claudication (n=28) were selected based on an appropriate history of peripheral arterial disease and intermittent claudication, ankle brachial pressure index <0.9 in at least 1 leg and a positive Edinburgh claudication questionnaire response. A further group of participants (n=25) free of peripheral arterial disease (ankle brachial pressure index >0.9) and who were non-regular exercisers were recruited from the community to act as age and mass matched controls. All participants underwent 2D angular kinematics analysis during normal walking. Intralimb coordination variability was measured using parameterization, vector coding and normalized root mean square techniques applied to relative motion plots of various joint couplings. Differences between groups were examined by one-way ANOVA., Findings: Participants with peripheral arterial disease and suffering from intermittent claudication displayed significantly greater intralimb joint coordination variability than age and mass matched controls participants for all joint couplings using all intralimb joint coordination variability techniques., Interpretation: These findings suggest that higher levels of intralimb joint coordination variability of the lower limbs in participants with peripheral arterial disease and suffering from intermittent claudication may be an adaptation of the motor control system to deal with perturbations associated with the gradual onset of claudication pain.

Objective: The purpose of the study was to examine the effects of a 12-month exercise program on lower limb mobility (temporal-spatial gait parameters and gait kinematics), walking performance, peak physiological responses, and physical activity levels in individuals with symptoms of intermittent claudication due to peripheral arterial disease (PAD-IC)., Methods: Participants (n = 21) with an appropriate history of PAD-IC, ankle-brachial pressure index (ABI) <0.9 in at least one leg and a positive Edinburgh claudication questionnaire response were prospectively recruited. Participants were randomly allocated to either a control PAD-IC group (CPAD-IC) (n = 11) that received standard medical therapy and a treatment PAD-IC group (TPAD-IC) (n = 10), which also took part in a 12-month supervised exercise program. A further group of participants (n = 11) free of PAD (ABI >0.9) and who were non-regular exercisers were recruited from the community to act as age and mass matched controls (CON). Lower limb mobility was determined via two-dimensional video motion analysis. A graded treadmill test was used to assess walking performance and peak physiological responses to exercise. Physical activity levels were measured via a 7-day pedometer recording. Differences between groups were analyzed via repeated measures analysis of variance (ANOVA)., Results: The 12-month supervised exercise program had no significant effect on lower limb mobility, peak physiological responses, or physical activity levels in TPAD-IC compared with CPAD-IC participants. However, the TPAD-IC participants demonstrated significantly greater walking performance (171% improvement in pain free walking time and 120% improvement in maximal walking time compared with baseline)., Conclusion: The results of this study confirm that a 12-month supervised exercise program will result in improved walking performance, but does not have an impact on lower limb mobility, peak physiological responses, or physical activity levels of PAD-IC patients.

Objective: Impaired physical function is a feature of patients with peripheral arterial disease (PAD) who present with symptoms of intermittent claudication (PAD-IC). Previous research found that temporal-spatial gait parameters do not discriminate between PAD-IC patients and control subjects during normal and maximal walking even though PAD-IC patients have decreased physical function characteristic of the disease. This study examined the hypothesis that patients with PAD-IC would demonstrate decreased temporal-spatial gait parameters, gait kinematics, walking performance, physiologic responses to exercise, and physical activity level compared with control subjects. The aim was to examine the temporal-spatial gait parameters and gait kinematics of individuals with PAD-IC and to determine the relationship between these variables and walking performance, exercise capacity, and physical activity level in these individuals., Method: A cross-sectional study of 28 PAD-IC subjects (IC) and 25 controls (CON) matched for age and mass was conducted in a medical faculty human performance laboratory. IC subjects had a history of PAD, ankle-brachial pressure index (ABI)<0.9 in at least one leg, and a positive Edinburgh Claudication Questionnaire response. Gait characteristics were determined by two-dimensional motion analysis. A graded treadmill test was used to assess walking performance and peak physiologic responses to exercise. Physical activity levels were measured by analysis of 7-day pedometer recording motion. Differences between groups were examined by one-way analysis of covariance., Results: Compared with CON, IC temporal-spatial gait parameters were significantly lower (P<.05), except for single support ipsilateral limb time. IC subjects spent a greater percentage of time in gait support phases, took longer to complete a stride, and had reduced stride length and walking speeds during the gait cycle. IC joint angular kinematics showed significantly reduced displacement of ankle plantar flexion (P=.017), knee range of motion (P=.021), and hip extension (P=.016) compared with the CON subjects during the gait cycle. All joint minimum and maximum angular velocities and accelerations, walking physiologic responses, and physical activity levels were significantly lower for IC compared with the CON subjects., Conclusion: IC subjects walk with a shuffling gait pattern indicated by reduced joint angular displacement, velocities, and accelerations that results in reduced walking performance and physiologic responses and physical activity compared with controls matched for age, mass, and physical activity.