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.

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 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 chronic venous disease with major adverse cardiovascular events.

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.

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.

Immunosuppressive drugs for nontransplant comorbidities are not associated with abdominal aortic aneurysm growth.

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.

Urgent Repair of a 17.3 cm Inflammatory Abdominal Aortic Aneurysm.

We describe a case of delayed presentation of a very large infra-renal inflammatory abdominal aortic aneurysm. This case highlights the importance of early detection and surveillance of aneurysms in rural communities. Definitive management of symptomatic aneurysms is time critical, and any delay such as for the transfer of patients from a rural site can impact patient survival. We present an example of a rare variant of abdominal aortic aneurysm.

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.

Cohort study examining the relationship between remoteness and requirement for surgery to treat peripheral artery disease at a tertiary hospital in North Queensland.

OBJECTIVE: To assess whether outcomes of peripheral artery disease (PAD) were related to remoteness from the treating tertiary vascular centre. SETTING AND PARTICIPANTS: Participants with a variety of types of occlusive and aneurysmal diseases were recruited from a tertiary hospital in North Queensland, Australia. Remoteness was assessed by residence outside Townsville and estimated distance to the vascular centre. Cox proportional hazard analyses were used to examine the association of remoteness with outcome. DESIGN: Cohort study. MAIN OUTCOME MEASURES: The primary outcome was requirement for surgery to treat PAD. Secondary outcomes were major adverse cardiovascular events (MACE) and all-cause mortality. RESULTS: Of 2487 patients recruited, 1274 (51.2%) had at least one PAD surgery, 720 (29.0%) at least one MACE, and 909 (36.6%) died during a median of 4.2 (inter-quartile range 1.3-7.7) years. Compared to Townsville residents (n = 1287), those resident outside Townsville (n = 1200) had higher rates of PAD surgery (hazard ratio, HR 1.55, 95% confidence intervals, CI, 1.39, 1.73) but no increased risk of MACE (HR 1.00, 95% CI 0.86, 1.16) or death (HR 1.03, 95% CI 0.90, 1.17). This association was attenuated when adjusting for distance from the vascular centre (HR 1.31, 95% CI 1.14, 1.51). Patients in the highest quartile of distance presented with lower ankle-brachial pressure index, more severe carotid artery disease and larger aortic diameter. CONCLUSIONS: People with PAD in North Queensland residing furthest from the tertiary hospital presented with more severe artery disease and had greater rates of PAD surgery.

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.

Outcomes and Costs of Open and Endovascular Revascularisation for Chronic Limb Ischaemia in an Australian Cohort.

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.

Survival following abdominal aortic aneurysm repair in North Queensland is not associated with remoteness of place of residence.

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.

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.

Randomized Placebo-Controlled Trial Assessing the Effect of 24-Week Fenofibrate Therapy on Circulating Markers of Abdominal Aortic Aneurysm: Outcomes From the FAME -2 Trial.

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.

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

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

Inositol in the MAnaGemENt of abdominal aortic aneurysm (IMAGEN): study protocol for a randomised controlled trial.

BACKGROUND: An abdominal aortic aneurysm (AAA) is a focal dilation of the abdominal aorta and is associated with a risk of fatal rupture. Experimental studies suggest that myo-inositol may exert beneficial effects on AAAs through favourable changes to biological pathways implicated in AAA pathology. The aim of the Inositol in the MAnaGemENt of abdominal aortic aneurysm (IMAGEN) trial is to assess if myo-inositol will reduce AAA growth. METHODS/DESIGN: IMAGEN is a multi-centre, prospective, parallel-group, randomised, double-blind, placebo-controlled trial. A total of 164 participants with an AAA measuring ≥ 30 mm will be randomised to either 2 g of myo-inositol or identical placebo twice daily for 12 months. The primary outcome measure will be AAA growth estimated by increase in total infrarenal aortic volume measured on computed tomographic scans. Secondary outcome measures will include AAA diameter assessed by computed tomography and ultrasound, AAA peak wall stress and peak wall rupture index, serum lipids, circulating AAA biomarkers, circulating RNAs and health-related quality of life. All analysis will be based on the intention-to-treat principle at the time of randomisation. All patients who meet the eligibility criteria, provide written informed consent and are enrolled in the study will be included in the primary analysis, regardless of adherence to dietary allocation. DISCUSSION: Currently, there is no known medical therapy to limit AAA progression. The IMAGEN trial will be the first randomised trial, to our knowledge, to assess the value of myo-inositol in limiting AAA growth. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12615001209583 . Registered on 6 November 2015.

Paclitaxel-coated balloon reduces target lesion revascularization compared with standard balloon angioplasty.

OBJECTIVE: Peripheral arterial disease (PAD) is a highly prevalent condition that contributes significantly to the morbidity and mortality of affected patients. PAD creates a significant economic burden on health care systems around the world. We reviewed all available literature to provide a meta-analysis assessing the outcome of patients treated with drug-eluting balloons (DEBs) compared with percutaneous transluminal balloon angioplasty (PTA) through measuring the rate of target lesion revascularization (TLR). METHODS: An electronic search of the MEDLINE, Scopus, Embase, Web of Science, and Cochrane Library databases was performed. Articles reporting randomized controlled trials that compared treatment with DEBs vs PTA were selected for inclusion. A meta-analysis was performed by pooling data on rates of TLR, binary restenosis (BR), and late lumen loss (LLL). RESULTS: The 10 included articles comprised a sample size of 1292 patients. Meta-analysis demonstrated the rate of TLR in DEB-treated patients was significantly lower compared with patients treated with PTA at 6 months (odds ratio [OR], 0.24; 95% confidence interval [CI], 0.11-0.53; P = .0004), 12 months (OR, 0.28; 95% CI, 0.13-0.62; P = .002), and 24 months (OR, 0.25; 95% CI, 0.10-0.61; P = .002). Decreased LLL and BR was demonstrated at 6 months in patients treated with DEBs compared with patients treated with PTA (mean difference, -0.74; 95% CI, -0.97 to -0.51; P = .00001; OR, 0.34; 95% CI, 0.23-0.49; P = .00001). CONCLUSIONS: This meta-analysis demonstrates that treatment with DEBs compared with PTA results in reduced rates of reintervention in patients with PAD. Comparison of DEBs to other emerging treatments to determine which method results in the lowest reintervention rates and in the greatest improvement in quality of life should be the focus of future trials.