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.

Rates of Stroke in Patients With Different Presentations of Carotid Artery Stenosis.

OBJECTIVE: Carotid artery stenosis may present without the classical symptoms of transient ischaemic attack or stroke but the rates of stroke for these presentations is unknown. The aim of this study was to examine the rates of stroke in patients with different presentations of carotid artery stenosis. METHODS: A multicentre prospective cohort study was conducted across three Australian vascular centres with low rates of surgical treatment of patients without transient ischaemic attack or stroke. Patients with a 50 - 99% carotid artery stenosis presenting with non-focal symptoms (e.g., dizziness or syncope; n = 47), prior contralateral carotid endarterectomy (n = 71), prior ipsilateral symptoms more than six months earlier (n = 82), and no symptoms (n = 304) were recruited. The primary outcome was ipsilateral ischaemic stroke. Secondary outcomes were any ischaemic stroke and cardiovascular death. Data were analysed using Cox proportional hazard and Kaplan-Meier analyses. RESULTS: Between 2002 and 2020, 504 patients were enrolled (mean age 71 years, 30% women) and followed for a median of 5.1 years (interquartile range 2.5, 8.8; 2 981 person years). Approximately 82% were prescribed antiplatelet therapy, 84% were receiving at least one antihypertensive drug, and 76% were prescribed a statin at entry. After five years the incidence of ipsilateral stroke was 6.5% (95% confidence interval [CI] 4.3 - 9.5). There were no statistically significant differences in the annual rate of ipsilateral stroke among people with non-focal symptoms (2.1%; 95% CI 0.8 - 5.7), prior contralateral carotid endarterectomy (0.2%; 0.03 - 1.6) or ipsilateral symptoms > 6 months prior (1.0%; 0.4 - 2.5) compared with those with no symptoms (1.2%; 0.7 - 1.8; p = .19). There were no statistically significant differences in secondary outcomes across groups. CONCLUSION: This cohort study showed no large differences in stroke rates among people with different presentations of carotid artery stenosis.

The predictive value of four serum biomarkers for major adverse events in patients with small abdominal aortic aneurysm.

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.

Venous cystic adventitial disease: to cure or manage? A case series.

Venous cystic adventitial disease is a rare vascular condition that can have significant effects on a patient's quality of life. The clinical presentation of venous cystic adventitial disease is variable, and there are no established guidelines on investigation or treatment of the disease. We present a series of three patients with venous cystic adventitial disease of the common femoral vein, treated within a single vascular surgery unit. Each of the three patients presented within 18 months of each other, despite the rarity of the disease. These are the only known cases treated within this vascular surgery unit. The investigation, management and treatment of each patient are individualised, with a management focus on quality of life.

Cohort Study Examining the Association of Immunosuppressant Drug Prescription With Major Adverse Cardiovascular and Limb Events in Patients With Peripheral Artery Disease.

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.

Association of Diagnosis of Depression and Small Abdominal Aortic Aneurysm Growth.

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.

Cohort Study Examining the Prevalence and Relationship with Outcome of Standard Modifiable Risk Factors in Patients with Peripheral Artery Occlusive and Aneurysmal Disease.

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.

Editor's Choice - Cohort Study Examining the Association Between Abdominal Aortic Size and Major Adverse Cardiovascular Events in Patients with Aortic and Peripheral Occlusive and Aneurysmal Disease.

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.

The Potential Benefits and Costs of an Intensified Approach to Low Density Lipoprotein Cholesterol Lowering in People with Abdominal Aortic Aneurysm.

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.

Control of modifiable risk factors and major adverse cardiovascular events in people with peripheral artery disease and diabetes.

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.

Relationship between requirement to stop during a six-minute walk test and health-related quality of life, physical activity and physical performance amongst people with intermittent claudication.

AIM: A simple objective test is required to identify people with impaired physical aspects of health-related quality of life (QOL) due to intermittent claudication. This study assessed the relationship of QOL, function and physical activity to the need to stop during a six-minute walking test (6MWT) amongst people with intermittent claudication. METHOD: This was a prospective case-control study conducted at two centers in Australia. 173 participants with a history of intermittent claudication and peripheral artery disease diagnosed by ankle brachial pressure index <0.9, completed two 6MWTs one week apart. QOL was assessed with the short form (SF)-36. Physical activity was assessed by an accelerometer to record step count, stepping time and energy expenditure over 7 days. Physical performance was assessed by the Short Physical Performance Battery (SPPB) test. The associations of the need to stop at least once during the 6MWT with QOL, function and activity were assessed using Mann Whitney U test and analysis of covariates. RESULTS: Participants that had to stop at least once during the two 6MWTs (46; 26.6%) had significantly lower scores for three of the domains (physical functioning, role-physical and bodily pain) and the physical component summary (PCS) measure of the SF-36 compared to those who did not need to stop (n = 127; 73.4%). After adjusting for the risk factor co-variates (diabetes, hypertension and ankle brachial pressure index) which were significantly unequally distributed, needing to stop during the 6MWTs was significantly associated with a lower PCS score (adjusted mean 36.5, standard error 0.8 vs. 30.5, standard error 1.3; F = 14.0; P < 0.001; partial eta squared 0.077). Participants that had to stop at least once during the two 6MWTs had significantly lower 7-day step count, time stepping and energy expenditure, but not total SPPB score, compared to those who did not need to stop. CONCLUSIONS: Needing to stop during a 6MWT identified participants with intermittent claudication with poorer QOL and less physical activity compared to those that do not need to stop.

The cost-effectiveness of intensive low-density lipoprotein cholesterol lowering in people with peripheral artery disease.

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.

A Randomised Controlled Trial Assessing the Effects of Peri-operative Fenofibrate Administration on Abdominal Aortic Aneurysm Pathology: Outcomes From the FAME Trial.

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.

Relationship Between Disease Specific Quality of Life Measures, Physical Performance, and Activity in People with Intermittent Claudication Caused by Peripheral Artery Disease.

OBJECTIVE: The aims of this study were firstly to assess the correlation between disease specific measures of quality of life (QOL) and physical performance and activity, and secondly to identify demographic, clinical, functional, and physical activity measures independently associated with QOL in people with intermittent claudication. METHODS: This was a cross sectional observational study of 198 people with intermittent claudication caused by peripheral artery disease who were recruited prospectively. QOL was assessed with the intermittent claudication questionnaire (ICQ) and the eight-theme peripheral artery disease quality of life questionnaire. Physical performance was assessed with the six minute walk test (6MWT) and short physical performance battery (SPPB), and an accelerometer was used to measure seven day step count. The associations between QOL scores and 6MWT distance, SPPB scores and seven day step count were examined using Spearman Rho's (ρ) correlation and multivariable linear regression. RESULTS: ICQ scores were significantly correlated with 6MWT distance (ρ = 0.472, p < .001), all four SPPB scores (balance ρ = 0.207, p = .003; gait speed ρ = 0.303, p < .001; chair stand ρ = 0.167, p = .018; total ρ = 0.265, p < .001), and seven day step count (ρ = 0.254, p < .001). PADQOL social relationships and interactions (ρ = 0.343, p < .001) and symptoms and limitations in physical functioning (ρ = 0.355, p < .001) themes were correlated with 6MWT distance. The 6MWT distance was independently positively associated with ICQ and both PADQOL theme scores (ICQ: B 0.069, p < .001; PADQOL social relationships and interactions: B 0.077, p < .001; PADQOL symptoms and limitations in physical functioning: B 0.069, p < .001). CONCLUSION: Longer 6MWT distance independently predicted better physical and social aspects of QOL in people with intermittent claudication supporting its value as an outcome measure.

Association of Serum Lipoprotein (a) With the Requirement for a Peripheral Artery Operation and the Incidence of Major Adverse Cardiovascular Events in People With Peripheral Artery Disease.

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.

Management of a large ruptured popliteal artery aneurysm involving combined deployment of a covered stent graft and evacuation of popliteal fossa hematoma.

Popliteal artery aneurysms (PAAs) are the most common of all peripheral aneurysms. However, ruptured PAA is rare, accounting for approximately 2% of PAA presentations. A literature review found only 11 published cases of ruptured PAAs treated with endovascular repair. In this case, a large (6.9 cm in diameter) ruptured PAA was successfully treated with endovascular repair using the GORE VIABAHN (W. L. Gore & Associates, Flagstaff, Ariz) stent graft and had simultaneous evacuation of popliteal fossa hematoma through a medial distal thigh incision. This facilitated more rapid recovery of mobility, reduced pain, and reduced hospital stay and may represent a useful hybrid surgical approach for this rare condition.

Editor's Choice - Metformin Prescription is Associated with a Reduction in the Combined Incidence of Surgical Repair and Rupture Related Mortality in Patients with Abdominal Aortic Aneurysm.

OBJECTIVES: Currently there is no drug therapy for abdominal aortic aneurysm (AAA) and most previous investigations have focused on imaging rather than clinical outcomes. The aim of this study was to assess whether AAA related clinical events were lower in patients prescribed metformin. METHODS: This was a prospective cohort observational study performed in three cities in Australia, which was designed to study risk factors for clinical events not simply to focus on metformin. Patients with an asymptomatic unrepaired AAA of any diameter ≥30 mm were recruited from hospital outpatient clinics and surveillance programs run at four centres. The main outcome was the requirement for AAA repair or AAA related mortality (AAA events). The association between metformin prescription and AAA events was assessed using Kaplan-Meier analysis and Cox proportional hazard analysis. RESULTS: Patients (1,080) with a mean (SD) initial AAA diameter of 46.1 (11.3) mm were followed for a mean (SD) of 2.5 (3.1) years until an AAA event (n = 454), death (n = 176), loss to follow up (n = 128), or completion of current follow up (n = 322). Patients with diabetes who were prescribed metformin (adjusted HR 0.63, 95% CI 0.44-0.93), but not patients with diabetes who were not prescribed metformin (adjusted HR 1.15, 95% CI 0.83-1.59), had a lower incidence of AAA events compared with those without diabetes. Findings were similar in sensitivity analyses restricted to patients with an initial AAA diameter ≤50 mm and patients with a minimum follow up of six months before an AAA event. CONCLUSIONS: These findings suggest that clinically important AAA events may be reduced in patients with diabetes who are prescribed metformin, but not those with diabetes receiving other treatments. A randomised controlled trial is needed to definitively test whether metformin reduces AAA related clinical events in patients with small AAAs who do not have diabetes.

Fenofibrate in the management of AbdoMinal aortic anEurysm (FAME): study protocol for a randomised controlled trial.

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.

Efficacy of brief behavioral counselling by allied health professionals to promote physical activity in people with peripheral arterial disease (BIPP): study protocol for a multi-center randomized controlled trial.

BACKGROUND: Physical activity is recommended for people with peripheral arterial disease (PAD), and can improve walking capacity and quality of life; and reduce pain, requirement for surgery and cardiovascular events. This trial will assess the efficacy of a brief behavioral counselling intervention delivered by allied health professionals to improve physical activity in people with PAD. METHODS: This is a multi-center randomised controlled trial in four cities across Australia. Participants (N = 200) will be recruited from specialist vascular clinics, general practitioners and research databases and randomised to either the control or intervention group. Both groups will receive usual medical care, a written PAD management information sheet including advice to walk, and four individualised contacts from a protocol-trained allied health professional over 3 months (weeks 1, 2, 6, 12). The control group will receive four 15-min telephone calls with general discussion about PAD symptoms and health and wellbeing. The intervention group will receive behavioral counselling via two 1-h face-to-face sessions and two 15-min telephone calls. The counselling is based on the 5A framework and will promote interval walking for 3 × 40 min/week. Assessments will be conducted at baseline, and 4, 12 and 24 months by staff blinded to participant allocation. Objectively assessed outcomes include physical activity (primary), sedentary behavior, lower limb body function, walking capacity, cardiorespiratory fitness, event-based claudication index, vascular interventions, clinical events, cardiovascular function, circulating markers, and anthropometric measures. Self-reported outcomes include physical activity and sedentary behavior, walking ability, pain severity, and health-related quality of life. Data will be analysed using an intention-to-treat approach. An economic evaluation will assess whether embedding the intervention into routine care would likely be value for money. A cost-effectiveness analysis will estimate change in cost per change in activity indicators due to the intervention, and a cost-utility analysis will assess change in cost per quality-adjusted life year. A full uncertainty analysis will be undertaken, including a value of information analysis, to evaluate the economic case for further research. DISCUSSION: This trial will evaluate the efficacy and cost-effectiveness of a brief behavioral counselling intervention for a common cardiovascular disease with significant burden. TRIAL REGISTRATION: ACTRN 12614000592640 Australian New Zealand Clinical Trials Registry. Registration Date 4 June 2014.