Peripheral arterial disease (PAD) - A challenging manifestation of atherosclerosis.

The diagnosis of peripheral arterial disease (PAD) is not always evident as symptoms and signs may show great variation. As all grades of PAD are linked to both an increased risk for cardiovascular complications and adverse limb events, awareness of the condition and knowledge about diagnostic measures, prevention and treatment is crucial. This article presents in a condensed form information on PAD and its management.

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

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

Estimating the diagnostic accuracy of the ankle-brachial pressure index for detecting peripheral arterial disease in people with diabetes: A systematic review and meta-analysis.

AIM: To systematically evaluate research investigating the accuracy of the ankle-brachial index (ABI) for diagnosing peripheral artery disease (PAD) in people with diabetes, as the accuracy is thought to be reduced in this cohort. METHODS: A database search of EBSCO Megafile Premier, Embase and The Cochrane Library was conducted to 28 February 2019. Prospective and retrospective investigations of the diagnostic accuracy of the ABI for PAD in people with diabetes using an imaging reference standard were eligible. Sensitivity and specify of the ABI and bivariate meta-analysis against reference tests, or a standard summary receiver operating curve analysis (SROC) was performed. RESULTS: Thirty-three studies met the inclusion criteria. ABI was compared with angiography in 12 studies and with colour duplex ultrasound (CDUS) in 21 studies. A SROC analysis of studies using angiography as the reference standard found a diagnostic odds ratio (DOR) of 9.06 [95% confidence interval (CI) 3.61 to 22.69], and area under the curve (AUC) of 0.76 (95% CI 0.66 to 0.86). Bivariate analysis of studies using CDUS demonstrated mean sensitivity of 0.60 (95% CI 0.48 to 0.71; P = 0.097) and mean specificity of 0.87 (95% CI 0.78 to 0.92; P < 0.001) with a DOR of 9.76 (95% CI 5.24 to 18.20; P < 0.0001) and AUC 0.72. CONCLUSIONS: These results suggest the ABI has a high specificity but lower sensitivity in detecting imaging diagnosed PAD in people with diabetes. The low probability of the testing being able to rule diagnosis in or out suggest that the ABI has limited effectiveness for early detection of PAD in this cohort.

Lack of an effective drug therapy for abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) rupture is a common cause of death in adults. Current AAA treatment is by open surgical or endovascular aneurysm repair. Rodent model and human epidemiology, and genetic and observational studies over the last few decades have highlighted the potential of a number of drug therapies, including medications that lower blood pressure, correct dyslipidaemia, or inhibit thrombosis, inflammation or matrix remodelling, as approaches to managing small AAA. This review summarizes prior AAA pathogenesis data from animal and human studies aimed at identifying targets for the development of drug therapies. The review also systematically assesses past randomized placebo-controlled drug trials in patients with small AAAs. Eleven previously published randomized-controlled clinical trials testing different drug therapies aimed at slowing AAA progression were identified. Five of the trials tested antibiotics and three trials assessed medications that lower blood pressure. Meta-analyses of these trials suggested that neither of these approaches limit AAA growth. Allocation to blood pressure-lowering medication was associated with a small reduction in AAA rupture or repair, compared to placebo (relative risk 0.94, 95% confidence intervals 0.89, 1.00, P = 0.047). Three further trials assessed the effect of a mast cell inhibitor, fibrate or platelet aggregation inhibition and reported no effect on AAA growth or clinical events. Past trials were noted to have a number of design issues, particularly small sample sizes and limited follow-up. Much larger trials are needed to properly test potential therapeutic approaches if a convincingly effective medical therapy for AAA is to be identified.

Meta-analyses of randomized controlled trials reporting the effect of home foot temperature monitoring, patient education or offloading footwear on the incidence of diabetes-related foot ulcers.

AIM: The aim of this study was to perform an up-to-date systematic review and meta-analysis of randomized controlled trials (RCTs) examining the efficacy of home foot temperature monitoring, patient education and offloading footwear in reducing the incidence of diabetes-related foot ulcers. METHODS: A literature search was performed using MEDLINE, PubMed, CINAHL, Scopus and Cochrane databases to identify relevant original studies. Meta-analyses were performed using intention-to-treat principals for worst (main analysis) and best (sub-analysis) case scenarios. Leave-one-out sensitivity analyses were used to assess the consistency of findings. RESULTS: Of 7575 unique records, 17 RCTs involving 2729 participants were included. Four tested home foot temperature monitoring (n = 468), six examined patient education (n = 823) and seven assessed offloading footwear (n = 1438). Participants' who performed home foot temperature monitoring [odds ratio (OR) 0.51, 95% confidence interval (CI) 0.31 to 0.84; n = 468] and those provided offloading footwear (OR 0.48, 95% CI 0.29 to 0.80; n = 1438) were less likely to develop a diabetes-related foot ulcer. Patient education programmes did not significantly reduce diabetes-related foot ulcer incidence (OR 0.59, 95% CI 0.29 to 1.20; n = 823). Sensitivity analyses suggested that offloading footwear findings were consistent, but home foot temperature findings were dependent on the individual inclusion of one trial. All RCTs had either high or unclear risk of bias. CONCLUSION: This meta-analysis suggests that offloading footwear is effective in reducing the incidence of diabetes-related foot ulcers. Home foot temperature monitoring also appears beneficial but larger trials are needed (PROSPERO registration no.: CRD42019135226).

Meta-analysis of clinical trials examining the benefit of structured home exercise in patients with peripheral artery disease.

BACKGROUND: Supervised exercise is recommended for the management of peripheral artery disease (PAD); however, the uptake is limited. Structured home exercise programmes may be more feasible, but their effectiveness is unclear. This systematic review and meta-analysis examined the benefit of structured home exercise programmes for treating PAD in comparison to controls not receiving an exercise programme. METHODS: A literature search was conducted to identify RCTs comparing structured home exercise with controls not receiving an exercise programme among patients with PAD. To be included, studies had to report outcomes from treadmill or corridor walking tests, or objective assessment of physical activity. Inverse variance-weighted meta-analysis was performed to compare changes in maximum walking distance and intermittent claudication onset distance in treadmill tests, walking distance during a 6-min walking test, and physical activity measured using a pedometer or accelerometer. Summarized results are presented in terms of standard deviation differences. RESULTS: Eleven randomized trials involving 807 patients were included. Follow-up ranged from 2 to 24 months; only one trial included follow-up beyond 12 months. Meta-analyses showed that structured home exercise programmes led to significant improvements in maximum walking distance (mean difference (MD) 0·32, 95 per cent c.i. 0·15 to 0·50; P < 0·001), intermittent claudication onset distance (MD 0·45, 0·27 to 0·62; P < 0·001), walking distance in a 6-min walking test (MD 0·28, 0·09 to 0·47; P = 0·004) and physical activity (MD 0·27, 0·11 to 0·43; P = 0·001). CONCLUSION: This meta-analysis suggests that structured home exercise programmes are effective at improving walking performance and physical activity in the short term for patients with PAD.

Systematic review and meta-analysis of clinical trials examining the effect of hyperbaric oxygen therapy in people with diabetes-related lower limb ulcers.

AIM: To examine the efficacy of hyperbaric oxygen therapy in healing diabetes-related lower limb ulcers through a meta-analysis of randomized clinical trials. METHODS: A literature search was conducted to identify appropriate clinical trials. Inclusion required randomized study design and reporting of the proportion of diabetes-related lower limb ulcers that healed. A meta-analysis was performed to examine the effect of hyperbaric oxygen therapy on ulcer healing. The secondary outcomes were minor and major amputations. RESULTS: Nine randomized trials involving 585 participants were included. People allocated to hyperbaric oxygen therapy were more likely to have complete ulcer healing (relative risk 1.95, 95% CI 1.51-2.52; P<0.001), and less likely to require major (relative risk 0.54, 95% CI 0.36-0.81; P=0.003) or minor (relative risk 0.68, 95% CI 0.48-0.98; P=0.040) amputations than control groups. Sensitivity analyses suggested the findings were dependent on the inclusion of one trial. Adverse events included ear barotrauma and a seizure. Many of the trials were noted to have methodological weaknesses including absence of blinding of outcome assessors, lack of a justifiable sample size calculation and limited follow-up. CONCLUSIONS: This meta-analysis suggests hyperbaric oxygen therapy improves the healing of diabetes-related lower limb ulcers and reduces the requirement for amputation. Confidence in these results is limited by significant design weaknesses of previous trials and inconsistent findings. A more rigorous assessment of the efficacy of hyperbaric the efficacy of hyperbaric oxygen therapy is needed.

Risk of major amputation in patients with intermittent claudication undergoing early revascularization.

BACKGROUND: Revascularization is being used increasingly for the treatment of intermittent claudication and yet few studies have reported the long-term outcomes of this strategy. The aim of this study was to compare the long-term outcome of patients with intermittent claudication who underwent revascularization compared with a group initially treated without revascularization. METHODS: Patients with symptoms of intermittent claudication and a diagnosis of peripheral arterial disease were recruited from outpatient clinics at three hospitals in Queensland, Australia. Based on variation in the practices of different vascular specialists, patients were either treated by early revascularization or received initial conservative treatment. Patients were followed in outpatient clinics using linked hospital admission record data. The primary outcome was the requirement for major amputation. Kaplan-Meier curves, Cox regression and competing risks analyses were used to compare major amputation rates. RESULTS: Some 456 patients were recruited; 178 (39·0 per cent) underwent early revascularization and 278 (61·0 per cent) had initial conservative treatment. Patients were followed for a mean(s.d.) of 5·00(3·37) years. The estimated 5-year major amputation rate was 6·2 and 0·7 per cent in patients undergoing early revascularization and initial conservative treatment respectively (P = 0·003). Early revascularization was associated with an increased requirement for major amputation in models adjusted for other risk factors (relative risk 5·40 to 4·22 in different models). CONCLUSION: Patients presenting with intermittent claudication who underwent early revascularization appeared to be at higher risk of amputation than those who had initial conservative treatment.

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

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

Meta-analysis of the association between peripheral artery disease and growth of abdominal aortic aneurysms.

BACKGROUND: The role of atherosclerosis in the pathogenesis of abdominal aortic aneurysm (AAA) is controversial. Atherosclerosis-associated peripheral artery disease (PAD) has been reported to be a risk factor for AAA in population screening studies; its relationship with AAA growth is controversial. METHODS: A systematic search of MEDLINE, Scopus, CINAHL and the Cochrane Central Register of Controlled Trials was conducted in April 2016 and repeated in January 2017. Databases were screened for studies reporting AAA growth rates in patients with, and without PAD. The included studies underwent quality assessment and, where possible, were included in the meta-analysis. A subgroup analysis was performed, including only studies that adjusted for confounding factors. RESULTS: Seventeen studies, including a total of 4873 patients, met the review entry criteria. Data from 15 studies were included in the meta-analysis. There was marked heterogeneity in study design, methodology and statistical analyses used. In the main analysis, PAD was associated with reduced AAA growth (mean difference - 0·13, 95 per cent c.i. -0·27 to -0·00; P = 0·04). However, statistical significance was not maintained in sensitivity analysis. In a subanalysis that included only data adjusted for other risk factors, no significant association between PAD and AAA growth was found (mean difference -0·11, -0·23 to 0·00; P = 0·05). CONCLUSION: This systematic review suggests that currently reported studies demonstrate no robust and consistent association between PAD and reduced AAA growth.

Association between metformin prescription and growth rates of abdominal aortic aneurysms.

BACKGROUND: It has been suggested that diabetes medications, such as metformin, may have effects that inhibit abdominal aortic aneurysm (AAA) growth. The aim of this study was to examine the association of diabetes treatments with AAA growth in three patient cohorts. METHODS: AAA growth was studied using ultrasound surveillance in cohort 1, repeated CT in cohort 2 and more detailed repeat CT in cohort 3. Growth was estimated by the mean annual increase in maximum AAA diameter. RESULTS: A total of 1697 patients with an AAA were studied, of whom 118, 39 and 16 patients were prescribed metformin for the treatment of diabetes in cohorts 1, 2 and 3 respectively. Prescription of metformin was associated with a reduced likelihood of median or greater AAA growth in all three cohorts (cohort 1: adjusted odds ratio (OR) 0·59, 95 per cent c.i. 0·39 to 0·87, P = 0·008; cohort 2: adjusted OR 0·38, 0·18 to 0·80, P = 0·011; cohort 3: adjusted OR 0·13, 0·03 to 0·61, P = 0·010). No other diabetes treatment was significantly associated with AAA growth in any cohort. CONCLUSION: These findings suggest a potential role for metformin in limiting AAA growth.

Profile of diabetes in men aged 79-97 years: the Western Australian Health in Men Study.

AIMS: To investigate behavioural, physical and biochemical characteristics associated with diabetes in the oldest age group of elderly men. METHODS: We conducted a cross-sectional analysis of community-dwelling men aged 79-97 years from Perth, Western Australia. Lifestyle behaviours, self-rated health, physical function, and fasting glucose and HbA1c levels were assessed. RESULTS: Of 1426 men, 315 had diabetes (22%). Men with diabetes were of similar age to men without (84.9 vs 84.5 years; P = 0.14). Only 26.5% of men with diabetes self-rated their health as excellent or very good, compared with 40.6% of men without diabetes (P < 0.001). Diabetes was associated with less involvement with recreational walking (32.7 vs 41.0%; P < 0.01) and leisure activities (19.0 vs 26.5%; P < 0.01). Men with diabetes had poorer physical function on multiple measures, including longer times for the Timed Up-and-Go test (15.0 ± 6.9 s vs 13.4 ± 5.3 s; P < 0.001) and weaker knee extension (20.2 vs 21.9 kg; P < 0.001). In multivariate analyses, diabetes was associated with an increased prevalence of myocardial infarction (odds ratio 1.80, 95% CI 1.25-2.60; P < 0.001) and falls resulting in injury (odds ratio 1.55, 95% CI 1.06-2.26; P = 0.02). Average HbA1c was 49 ± 8 mmol/mol (6.6 ± 0.8%) in men with diabetes, with 90.6% of these men on diet or oral hypoglycaemic therapy. CONCLUSIONS: In older men, diabetes is associated with poorer self-perceived health, reduced healthy lifestyle behaviours and physical function, heart disease and injurious falls. The majority of these men with diabetes had good glycaemic control. Encouraging healthy lifestyle behaviours and improving physical function should be evaluated as interventions to improve quality-of-life and health outcomes.

Systematic Review and Meta-Analysis of the Association Between C-Reactive Protein and Major Cardiovascular Events in Patients with Peripheral Artery Disease.

BACKGROUND: Patients with peripheral artery disease (PAD) are at substantial risk of cardiovascular events. There is interest in using blood markers, such as C-reactive protein (CRP), to monitor prognosis and treatment efficacy in PAD patients. The aim of this meta-analysis was to assess the association between CRP and major cardiovascular events in PAD patients. METHOD: Studies evaluating the association between CRP and major cardiovascular events (myocardial infarction, stroke, cardiac revascularisation and mortality) were identified using MEDLINE and the Cochrane library. Studies that did not include participants with PAD, measure CRP, or follow-up patients for cardiovascular events were excluded. Meta-analyses of published adjusted hazard ratios (HR) were conducted using an inverse variance-weighted random effects model, and heterogeneity was assessed with the I2 index. RESULTS: A total of 16 studies involving 5041 participants met the inclusion criteria for the systematic review. Eight studies were included in the meta-analyses. Summary effect estimates were reported as HR comparing higher and lower quantiles, and HR per unit increase in logeCRP. PAD patients with higher CRP had a significantly greater risk of major cardiovascular events compared with those with lower CRP (HR 2.26, 95% CI 1.65-3.09, p < 0.001). The HR for major cardiovascular events was 1.38 (95% CI 1.16-1.63, p < 0.001) per unit increase in logeCRP. CONCLUSIONS: The present findings suggest that high circulating CRP is predictive of major cardiovascular events in PAD patients.

The Consequences of Real Life Practice of Early Abdominal Aortic Aneurysm Repair: A Cost-Benefit Analysis.

BACKGROUND: The reported 54 mm median intervention diameter for endovascular aneurysm repair (EVAR) in the Vascular Quality Initiative and European data from the Pharmaceutical Aneurysm Stabilisation Trial (PHAST) implies that in real life the majority of abdominal aortic aneurysm (AAA) repairs occur at diameters smaller than the consensus intervention threshold of 55 mm. This study explores the potential consequences of this practice. METHODS: The differences between real life AAA repair and consensus based intervention threshold were explored in reported data from vascular quality initiatives and PHAST. The subsequent consequences of advancement of endovascular aneurysm repair (EVAR) were estimated using a multistate model based on life tables for the EVAR Medicare population. RESULTS: There appears an approximate 5 mm difference in AAA diameter between real life practice and consensus intervention threshold. Assuming a 2.5 mm annual growth rate, this results in an approximately 2 year advancement of AAA repair. According to the model used, early repair reduces overall small aneurysm patient mortality by 2.3%, it results in 21.9% more EVAR procedures, more EVAR related deaths, and 42.3% and 36.8% more open and endovascular re-interventions, respectively. Cost-benefit estimates imply 482 fewer AAA related deaths, but 140 extra EVAR related deaths for a population of more than 30,000 AAA patients, and a 300 million USD increase in health costs for the 8 year observation period in the Medicare population. CONCLUSIONS: In the real life situation a large proportion of EVAR procedures appear to occur before reaching the consensus threshold. Although this reduces mortality, it comes at a cost of approximately 1 million USD per prevented rupture related death.

The triangular association of ADH1B genetic polymorphism, alcohol consumption and the risk of depression in older men.

Alcohol use, particularly alcohol abuse and dependence, are associated with increased risk of depression. Current diagnostic criteria suggest that the relationship is causal, but the evidence has only been derived from observational studies that are subject to confounding and bias. Given the logistic and ethical constraints that would be associated with a trial of alcohol use to prevent depression, we aimed to complete a Mendelian randomization study to determine if a genetic polymorphism associated with alcohol abuse and dependence (ADH1B rs1229984 G-->A) contributed to modulate the risk of depression in a community-derived cohort of older men. This retrospective analysis of a cohort of 3873 community-dwelling men aged 65-83 years living in the metropolitan region of Perth, Western Australia, investigated the triangular association between the rs1229984 G-->A polymorphism and alcohol use and, after 3.2-8.2 years, the presence of current depression or history of depression. The mean number of standard drinks consumed per week (n; standard deviation; range) according to genotype was AA 1.8 (17; 2.7; 0-7), GA 5.9 (262; 7.5; 0-35), GG 8.5 (3594; 10.9; 0-140) (GG>AA, GG>GA; P<0.001). Consumption of 1 or 2 drinks per day decreased the odds of depression (n=610) by 30 and 40%, whereas consumption of more than six drinks daily more than doubled the odds of depression (odds ratio: 2.12, 95% confidence interval: 1.02, 4.40). The ADH1B rs1229984 G-->A polymorphism was not associated with current or past depression (P=0.857). In addition, the presence of the A allele did not interact with the alcohol use to modulate the risk of depression (P=0.725). These results suggest that alcohol consumption does not cause or prevent depression in older men.

Effect of statin therapy on plasma proprotein convertase subtilisin kexin 9 (PCSK9) concentrations: a systematic review and meta-analysis of clinical trials.

AIMS: To evaluate the magnitude of the effect of statin therapy on plasma proprotein convertase subtilisin kexin 9 (PCSK9) levels through a systematic review and meta-analysis of clinical trials. METHODS: A random-effects model (using DerSimonian-Laird method) and the generic inverse variance method were used for quantitative data synthesis. Heterogeneity was quantitatively assessed using the I(2) index. Sensitivity analyses were conducted using the one-study remove approach. Random-effects meta-regression was performed using an unrestricted maximum likelihood method to evaluate the association between statin-induced elevation of plasma PCSK9 concentrations with duration of treatment and magnitude of LDL cholesterol reduction. RESULTS: A total of 15 clinical trials examining the effects of statin therapy on plasma PCSK9 levels were included. Meta-analysis of data from single-arm statin treatment arms [weighted mean difference (WMD) 40.72 ng/ml, 95% confidence interval (CI) 34.79, 46.65; p < 0.001] and randomized placebo-controlled trials (WMD 22.98 ng/ml, 95% CI 17.95, 28.01; p < 0.001) showed a significant increase in plasma PCSK9 concentrations after statin therapy, irrespective of the type of statin administered in either of the analyses (single-arm or randomized placebo-controlled trial). There was no significant elevation of plasma PCSK9 levels with statin/ezetimibe combination therapy compared with statin monotherapy (WMD 23.14 ng/ml, 95% CI -1.97, 48.25; p = 0.071); however, removal of one study in the meta-analysis yielded a significant result in the sensitivity analysis (WMD 31.41 ng/ml, 95% CI 7.86, 54.97; p = 0.009). CONCLUSIONS: This meta-analysis suggests that statin therapy causes a significant increase in plasma PCSK9 concentrations.

Plasma Low-density Lipoprotein Receptor-related Protein 1 Concentration is not Associated with Human Abdominal Aortic Aneurysm Presence.

OBJECTIVE/BACKGROUND: Recent genetic data suggest that a polymorphism of LRP1 is an independent risk factor for abdominal aortic aneurysm (AAA). The aims of this study were to assess whether plasma and aortic concentrations of low-density lipoprotein receptor-related protein 1 (LRP1) are associated with AAA, and to investigate the possible relevance of LRP1 to AAA pathophysiology. METHODS: Three analyses were conducted. First, plasma LRP1 concentrations were measured in community-dwelling men with and without AAA (n = 189 and n = 309, respectively) using enzyme-linked immunosorbent assay. Second, Western blotting analyses were employed to compare the expression of LRP1 protein in aortic biopsies collected from patients with AAA and nonaneurysmal postmortem donors (n = 6/group). Finally, the effect of in vitro LRP1 blockade on matrix metalloprotease 9 (MMP9) clearance by vascular smooth muscle cells was assessed by zymography. RESULTS: Plasma LRP1 concentrations did not differ between groups of men with and without AAA (median concentration 4.56 µg/mL [interquartile range {IQR} (3.39-5.96)] and 4.43 µg/mL [IQR 3.44-5.84], respectively; p = .48), and were not associated with AAA after adjusting for other risk factors (odds ratio 1.10 [95% confidence interval: 0.91-1.32]; p = 0.35). In contrast, LRP1 expression was approximately 3.4-fold lower in aortic biopsies recovered from patients with AAA compared with controls (median [IQR] expression 1.72 [0.94-3.14] and 5.91 [4.63-6.94] relative density units, respectively; p < .01). In vitro LRP1 blockade significantly reduced the ability of vascular smooth muscle cells to internalize extracellular MMP9. CONCLUSIONS: These data suggest that aortic but not circulating LRP1 is downregulated in patients with AAA and indicates a possible role for this protein in clearing an aneurysm-relevant ligand.

Meta-analysis of peak wall stress in ruptured, symptomatic and intact abdominal aortic aneurysms.

BACKGROUND: Abdominal aortic aneurysm (AAA) is an important cause of sudden death; however, there are currently incomplete means to predict the risk of AAA rupture. AAA peak wall stress (PWS) can be estimated using finite element analysis (FEA) methods from computed tomography (CT) scans. The question is whether AAA PWS can predict AAA rupture. The aim of this systematic review was to compare PWS in patients with ruptured and intact AAA. METHODS: The MEDLINE database was searched on 25 May 2013. Case-control studies assessing PWS in asymptomatic intact, and acutely symptomatic or ruptured AAA from CT scans using FEA were included. Data were extracted independently. A random-effects model was used to calculate standard mean differences (SMDs) for PWS measurements. RESULTS: Nine studies assessing 348 individuals were identified and used in the meta-analysis. Results from 204 asymptomatic intact and 144 symptomatic or ruptured AAAs showed that PWS was significantly greater in the symptomatic/ ruptured AAAs compared with the asymptomatic intact AAAs (SMD 0·95, 95 per cent confidence interval 0·71 to 1·18; P < 0·001). The findings remained significant after adjustment for mean systolic blood pressure, standardized at 120 mmHg (SMD 0·68, 0·39 to 0·96; P < 0·001). Minimal heterogeneity between studies was noted (I(2) = 0 per cent). CONCLUSION: This study suggests that PWS is greater in symptomatic or ruptured AAA than in asymptomatic intact AAA.