Mortality with Paclitaxel-Coated Devices in Peripheral Artery Disease.

BACKGROUND: The results of a recent meta-analysis aroused concern about an increased risk of death associated with the use of paclitaxel-coated angioplasty balloons and stents in lower-limb endovascular interventions for symptomatic peripheral artery disease. METHODS: We conducted an unplanned interim analysis of data from a multicenter, randomized, open-label, registry-based clinical trial. At the time of the analysis, 2289 patients had been randomly assigned to treatment with drug-coated devices (the drug-coated-device group, 1149 patients) or treatment with uncoated devices (the uncoated-device group, 1140 patients). Randomization was stratified according to disease severity on the basis of whether patients had chronic limb-threatening ischemia (1480 patients) or intermittent claudication (809 patients). The single end point for this interim analysis was all-cause mortality. RESULTS: No patients were lost to follow-up. Paclitaxel was used as the coating agent for all the drug-coated devices. During a mean follow-up of 2.49 years, 574 patients died, including 293 patients (25.5%) in the drug-coated-device group and 281 patients (24.6%) in the uncoated-device group (hazard ratio, 1.06; 95% confidence interval, 0.92 to 1.22). At 1 year, all-cause mortality was 10.2% (117 patients) in the drug-coated-device group and 9.9% (113 patients) in the uncoated-device group. During the entire follow-up period, there was no significant difference in the incidence of death between the treatment groups among patients with chronic limb-threatening ischemia (33.4% [249 patients] in the drug-coated-device group and 33.1% [243 patients] in the uncoated-device group) or among those with intermittent claudication (10.9% [44 patients] and 9.4% [38 patients], respectively). CONCLUSIONS: In this randomized trial in which patients with peripheral artery disease received treatment with paclitaxel-coated or uncoated endovascular devices, the results of an unplanned interim analysis of all-cause mortality did not show a difference between the groups in the incidence of death during 1 to 4 years of follow-up. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT02051088.).

Semi-Conservative Treatment Versus Radical Surgery in Abdominal Aortic Graft and Endograft Infections.

OBJECTIVE: Abdominal aortic graft and endograft infections (AGIs) are rare complications following aortic surgery. Radical surgery (RS) with resection of the infected graft and reconstruction with extra-anatomical bypass or in situ reconstruction is the preferred therapy. For patients unfit for RS, a semi-conservative (SC), graft preserving strategy is possible. This paper aimed to compare survival and infection outcomes between RS and SC treatment for AGI in a nationwide cohort. METHODS: Patients with abdominal AGI related surgery in Sweden between January 1995 and May 2017 were identified. The Management of Aortic Graft Infection Collaboration (MAGIC) criteria were used for the definition of AGI. Multivariable regression was performed to identify factors associated with mortality. RESULTS: One hundred and sixty-nine patients with surgically treated abdominal AGI were identified, comprising 43 SC (14 endografts; 53% with a graft enteric fistula [GEF] in total) and 126 RS (26 endografts; 50% with a GEF in total). The SC cohort was older and had a higher frequency of cardiac comorbidities. There was a non-significant trend towards lower Kaplan-Meier estimated five year survival for SC vs. RS (30.2% vs. 48.4%; p = .066). A non-significant trend was identified towards worse Kaplan-Meier estimated five year survival for SC patients with a GEF vs. without a GEF (21.7% vs. 40.1%; p = .097). There were significantly more recurrent graft infections comparing SC with RS (45.4% vs. 19.3%; p < .001). In a Cox regression model adjusting for confounders, there was no difference in five year survival comparing SC vs. RS (HR 1.0, 95% CI 0.6 - 1.5). CONCLUSION: In this national AGI cohort, there was no mortality difference comparing SC and RS for AGI when adjusting for comorbidities. Presence of GEF probably negatively impacts survival outcomes of SC patients. Rates of recurrent infection remain high for SC treated patients.

Impact of walk advice alone or in combination with supervised or home-based structured exercise on patient-reported physical function and generic and disease-specific health related quality of life in patients with intermittent claudication, a secondary analysis in a randomized clinical trial.

BACKGROUND: Supervised exercise is an integral part of the recommended first-line treatment for patients with intermittent claudication (IC). By reflecting the patients' perspectives, patient-reported outcome measurements provide additional knowledge to the biomedical endpoints and are important outcomes to include when evaluating exercise interventions in patients with IC. We aimed to evaluate the one-year impact of three strategies: unsupervised Nordic pole walk advice (WA), WA + six months of home-based structured exercise (HSEP) or WA + six months of hospital-based supervised exercise (SEP) on health-related quality of life and patient-reported physical function in patients with IC. METHODS: This secondary exploratory analysis of a multi-center, randomized clinical trial compared three exercise strategies. The primary outcome of the secondary analysis was the one-year change in the 36-Item Short-Form (SF-36). Secondary outcomes were three- and six-months SF-36 changes alongside three, six- and 12-months changes in the disease-specific Vascular Quality of Life instrument (VascuQoL) and the Patient-Specific Functional Scale (PSFS). The Kruskal-Wallis test with Bonferroni-adjusted post-hoc tests were used for between-group comparisons. Effect size calculations were used to describe the size of observed treatment effects, and the clinical meaningfulness of observed changes in the VascuQoL summary score at one year was studied using established minimally important difference (MID) thresholds. RESULTS: A total of 166 patients with IC, mean age: 72.1 (SD 7.4) years, 41% women, were randomized. No significant between-group differences were observed over time for the SF-36 or the PSFS scores whereas some significant between-group differences were observed in the VascuQoL domain and summary scores over time, favoring SEP and/or HSEP over WA. The observed SF-36 and VascuQoL domain and summary score effect sizes were small to moderate, and many domain score effect sizes also remained unchanged over time. A significantly higher proportion of the patients in the SEP group reached the VascuQoL summary score MID of improvement in one year. CONCLUSION: Clinically important improvements were observed in SEP using the VascuQoL, while we did not observe any significant between-group differences using the SF-36. Whereas effect sizes for the observed changes over time were generally small, a significantly higher proportion of patients in SEP reached the VascuQoL MID of improvement. TRIAL REGISTRATION: NCT02341716, January 19, 2015 (retrospectively registered).

Impact of Ankle Brachial Index Calculations on Peripheral Arterial Disease Prevalence and as a Predictor of Cardiovascular Risk.

OBJECTIVE: The aim of this study was to estimate the prevalence and predictive accuracy for cardiovascular (CV) morbidity by using different ankle brachial index (ABI) calculation methods in the general population. METHODS: ABI measurements and questionnaire data were collected from 5 080 randomly selected citizens aged 60 - 90 years. A 10 year follow up with data from Swedish national health registries was carried out. ABI was calculated using as numerator the highest (ABI-HI) or the lowest (ABI-LO) ankle BP obtained in each leg. Subjects were defined as references or having peripheral arterial disease (PAD) based on ABI-LO (Group 1) or ABI-HI (Group 2). Prevalence, mortality, CV events and risk were then analysed for these three groups, and their predictive power by using the area under the curve (AUC). RESULTS: A total of 4 909 inhabitants were included in the cohort (References: 83.8%, Group 1: 6.7% and Group 2: 9.6%). The prevalence of PAD was 16% using ABI-LO, and 9.6% using ABI-HI. The 10 year all cause mortality for references and Groups 1 and 2 was 27.6%, 48.8%, and 67.2%, respectively. The overall age adjusted hazard ratio (95% confidence interval) for the composite outcome of CV mortality and a non-fatal CV event was 1.25 (1.06 - 1.49) for Group 1 and 2.11 (1.85 - 2.39) for Group 2. The prediction accuracy for ABI < 0.9 in predicting CV event measured with AUC was 0.60 for ABI-HI and 0.62 for ABI-LO. CONCLUSION: An ABI < 0.9 should be considered a strong risk marker for future CV morbidity. Applying the traditional ABI calculation method of using the highest measured ankle BP, a group of subjects with high CV risk may be overlooked for intervention, and this why the lowest ankle BP should be the preferred for risk stratification. However, as a single predictive tool an ABI < 0.9 cannot adequately discriminate which individual will have a future CV event regardless of calculation method used.

A Delphi Consensus on Patient Reported Outcomes for Registries and Trials Including Patients with Intermittent Claudication: Recommendations and Reporting Standard.

OBJECTIVE: This study aimed to develop a core set of patient reported outcome quality indicators (QIs) for the treatment of patients with intermittent claudication (IC), that allow a broad international implementation across different vascular registries and within trials. METHODS: A rigorous modified two stage Delphi technique was used to promote consensus building on patient reported outcome QIs among an expert panel consisting of international vascular specialists, patient representatives, and registry members of the VASCUNET and the International Consortium of Vascular Registries. Potential QIs identified through an extensive literature search or additionally proposed by the panel were validated by the experts in a preliminary survey and included for evaluation. Consensus was reached if ≥ 80% of participants agreed that an item was both clinically relevant and practical. RESULTS: Participation rates in two Delphi rounds were 66% (31 participants of 47 invited) and 90% (54 of 60), respectively. Initially, 145 patient reported outcome QIs were documented. Following the two Delphi rounds, 18 quality indicators remained, all of which reached consensus regarding clinical relevance. The VascuQoL questionnaire (VascuQoL-6), currently the most common patient reported outcome measurement (PROM) used within vascular registries, includes a total of six items. Five of these six items also matched with high rated indicators identified in the Delphi study. Consequently, the panel recommends the use of the VascuQoL-6 survey as a preferred core PROM QI set as well as an optional extension of 12 additional patient reported QIs that were also identified in this study. CONCLUSION: The current recommendation based on the Delphi consensus building approach, strengthens the international harmonisation of registry data collection in relation to patient reported outcome quality. Continuous and standardised quality assurance will ensure that registry data may be used for future quality benchmarking studies and, ultimately, positively impact the overall quality of care provided to patients with peripheral arterial occlusive disease.

Editor's Choice - Outcome of Radical Surgical Treatment of Abdominal Aortic Graft and Endograft Infections Comparing Extra-anatomic Bypass with In Situ Reconstruction: A Nationwide Multicentre Study.

OBJECTIVE: Abdominal aortic graft and endograft infection (AGI) is primarily treated by resection of the infected graft and restoration of distal perfusion through extra-anatomic bypass (EAB) or in situ reconstruction/repair (ISR). The aim of this study was to compare these surgical strategies in a nationwide multicentre retrospective cohort study. METHODS: The Swedish Vascular Registry (Swedvasc) was used to identify surgically treated abdominal AGIs in Sweden between January 1995 and May 2017. The primary aim was to compare short and long term survival, as well as complications for EAB and ISR. RESULTS: Some 126 radically surgically treated AGI patients were identified - 102 graft infections and 24 endograft infections - treated by EAB: 71 and ISR: 55 (23 neo-aorto-iliac systems, NAISs). No differences in early 30 day (EAB 81.7% vs. ISR 76.4%, p = .46), or long term five year survival (48.2% vs. 49.9%, p = .87) were identified. There was no survival difference comparing NAIS to other ISR strategies. The frequency of recurrent graft infection during follow up was similar: EAB 20.3% vs. ISR 17.0% (p = .56). Survival and re-infection rates of the new conduit did not differ between NAIS and other ISR strategies. Age ≥ 75 years (odds ratio [OR] 4.0, confidence interval [CI] 1.1 - 14.8), coronary artery disease (OR 4.2, CI 1.2 - 15.1) and post-operative circulatory complications (OR 5.2, CI 1.2 - 22.5) were associated with early death. Prolonged antimicrobial therapy (> 3 months) was associated with reduced long term mortality (HR 0.3, CI 0.1 - 0.9). CONCLUSION: In this nationwide multicentre study comparing outcomes of radically treated AGI, no differences in survival or re-infection rate could be identified comparing EAB and ISR.

Editor's Choice - International Variations and Sex Disparities in the Treatment of Peripheral Arterial Occlusive Disease: A Report from VASCUNET and the International Consortium of Vascular Registries.

OBJECTIVE: The aim of this study was to determine sex specific differences in the invasive treatment of symptomatic peripheral arterial occlusive disease (PAOD) between member states participating in the VASCUNET and International Consortium of Vascular Registries. METHODS: Data on open surgical revascularisation and peripheral vascular intervention (PVI) of symptomatic PAOD from 2010 to 2017 were collected from population based administrative and registry data from 11 countries. Differences in age, sex, indication, and invasive treatment modality were analysed. RESULTS: Data from 11 countries covering 671 million inhabitants and 1 164 497 hospitalisations (40% women, mean age 72 years, 49% with intermittent claudication, 54% treated with PVI) in Europe (including Russia), North America, Australia, and New Zealand were included. Patient selection and treatment modality varied widely for the proportion of female patients (23% in Portugal and 46% in Sweden), the proportion of patients with claudication (6% in Italy and 69% in Russia), patients' mean age (70 years in the USA and 76 years in Italy), the proportion of octogenarians (8% in Russia and 33% in Sweden), and the proportion of PVI (24% in Russia and 88% in Italy). Numerous differences between females and males were observed in regard to patient age (72 vs. 70 years), the proportion of octogenarians (28% vs. 15%), proportion of patients with claudication (45% vs. 51%), proportion of PVI (57% vs. 51%), and length of hospital stay (7 days vs. 6 days). CONCLUSION: Remarkable differences regarding the proportion of peripheral vascular interventions, patients with claudication, and octogenarians were seen across countries and sexes. Future studies should address the underlying reasons for this, including the impact of national societal guidelines, reimbursement, and differences in health maintenance.

Editor's Choice - Recommendations for Registry Data Collection for Revascularisations of Acute Limb Ischaemia: A Delphi Consensus from the International Consortium of Vascular Registries.

OBJECTIVE: To develop a minimum core data set for evaluation of acute limb ischaemia (ALI) revascularisation treatment and outcomes that would enable collaboration among international registries. METHODS: A modified Delphi approach was used to achieve consensus among international multidisciplinary vascular specialists and registry members of the International Consortium of Vascular Registries (ICVR). Variables identified in the literature or suggested by the expert panel, and variables, including definitions, currently used in 15 countries in the ICVR, were assessed to define both a minimum core and an optimum data set to register ALI treatment. Clinical relevance and practicability were both assessed, and consensus was defined as ≥ 80% agreement among participants. RESULTS: Of 40 invited experts, 37 completed a preliminary survey and 31 completed the two subsequent Delphi rounds via internet exchange and face to face discussions. In total, 117 different items were generated from the various registry data forms, an extensive review of the literature, and additional suggestions from the experts, for potential inclusion in the data set. Ultimately, 35 items were recommended for inclusion in the minimum core data set, including 23 core items important for all registries, and an additional 12 more specific items for registries capable of capturing more detail. These 35 items supplement previous data elements recommended for registering chronic peripheral arterial occlusive disease treatment. CONCLUSION: A modified Delphi study allowed 37 international vascular registry experts to achieve a consensus recommendation for a minimum core and an optimum data set for registries covering patients who undergo ALI revascularisation. Continued global harmonisation of registry infrastructure and definition of items allows international comparisons and global quality improvement. Furthermore, it can help to define and monitor standards of care and enable international research collaboration.

Ten Year Mortality in Different Peripheral Arterial Disease Stages: A Population Based Observational Study on Outcome.

OBJECTIVE: The aim was to determine long-term mortality rates and the underlying cause of death for subjects with different peripheral arterial disease (PAD) stages in a population based setting. METHODS: A randomly selected population sample of 5080 subjects was enrolled in the study in 2004-2005. Participants completed health state questionnaires and underwent ankle brachial index (ABI) measurements for classification into PAD severity stages and reference subjects. A follow-up was conducted by the end of 2015 using data from Swedish governmental national registers for cause of death, which was then compared with PAD stage determined at baseline in 2005. RESULTS: The 10 year all cause mortality was 27% for reference cases, 56% for asymptomatic PAD (APAD), 63% for intermittent claudication (IC), and 75% for severe limb ischaemia (SLI). Among all PAD subjects, cardiovascular (CV) causes were the most common main cause of death (45%) and a CV event was present as either the main or one of the three most common contributing causes of death in 64% of the cases. The age adjusted hazard ratios for a main cause of death by a CV event were 1.9 (95% CI 1.5-2.3) for APAD, 2.6 (95% CI 2.1-3.4) for IC, and 3.5 (95% CI 2.3-5.2) for SLI. CONCLUSION: PAD subjects, including the APAD subjects, are still at high risk of CV death. The mortality risks are more than doubled in symptomatic PAD patients compared with reference subjects and increase by severity of PAD stage. Awareness and improved risk reduction management of PAD are still warranted.

Editor's Choice - Impact of Comorbidity, Medication, and Gender on Amputation Rate Following Revascularisation for Chronic Limb Threatening Ischaemia.

OBJECTIVE/BACKGROUND: Chronic limb threatening ischaemia (CLTI) has a high risk of amputation and mortality. Increased knowledge on how sex, comorbidities, and medication influence these outcomes after revascularisation may help optimise results and patient selection. METHODS: This population based observational cohort study included all individuals revascularised for CLTI in Sweden during a five year period (10,617 patients in total). Data were retrieved and merged from mandatory national healthcare registries, and specifics on amputations were validated with individual medical records. RESULTS: Mean age at revascularisation was 76.8 years. Median follow up was 2.7 years (range 0-6.6 years). Male sex (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.09-1.33), renal insufficiency (HR 1.57, 95% CI 1.32-1.87), diabetes (HR 1.45, 95% CI 1.32-1.60), and heart failure (HR 1.17, 95% CI 1.05-1.31) were independently associated with an increased amputation rate, whereas the use of statins (HR 0.71, 95% CI 0.64-0.78) and low dose acetylsalicylic acid (HR 0.77, 95% CI 0.70-0.86) were associated with a reduced amputation rate. For the combined end point of amputation or death, an association with increased rates was found for male sex (HR 1.25, 95% CI 1.18-1.32), renal insufficiency (HR 1.94, 95% CI 1.75-2.14), heart failure (HR 1.50, 95% CI 1.40-1.60), and diabetes (HR 1.31, 95% CI 1.23-1.38). The use of statins (HR 0.74, 95% CI 0.67-0.82) and low dose acetylsalicylic acid (HR 0.82, 95% CI 0.77-0.88]) were related to a reduced risk of amputation or death. CONCLUSIONS: Renal insufficiency is the strongest independent risk factor for both amputation and amputation/death in revascularised CLTI patients, followed by diabetes and heart failure. Men with CLTI have worse outcomes than women. These results may help govern patient selection for revascularisation procedures. Statin and low dose acetylsalicylic acid are associated with an improved limb outcome. This underlines the importance of preventive medication to reduce general cardiovascular risk and increase limb salvage.

International Variations in Amputation Practice: A VASCUNET Report.

OBJECTIVES: To study international differences in incidence and practice patterns as well as time trends in lower limb amputations related to peripheral arterial disease and/or diabetes mellitus. METHODS: Data on lower limb amputations during 2010-2014 were collected from population based administrative data from countries in Europe and Australasia participating in the VASCUNET collaboration. Amputation rates, time trends, in hospital or 30 day mortality and reimbursement systems were analysed. RESULTS: Data from 12 countries covering 259 million inhabitants in 2014 were included. Individuals aged ≥ 65 years ranged from 12.9% (Slovakia) to 20.7% (Germany) and diabetes prevalence among amputees from 25.7% (Finland) to 74.3% (Slovakia). The mean incidence of major amputation varied between 7.2/100,000 (New Zealand) and 41.4/100,000 (Hungary), with an overall declining time trend with the exception of Slovakia, while minor amputations increased over time. The older age group (≥65 years) was up to 4.9 times more likely to be amputated compared with those younger than 65 years. Reported mortality rates were lowest in Finland (6.3%) and highest in Hungary (20.3%). Countries with a fee for service reimbursement system had a lower incidence of major amputation compared with countries with a population based reimbursement system (14.3/100,000 versus 18.4/100,000, respectively, p < .001). CONCLUSIONS: This international audit showed large geographical differences in major amputation rates, by a factor of almost six, and an overall declining time trend during the 4 year observation of this study. Diabetes prevalence, age distribution, and mortality rates were also found to vary between countries. Despite limitations attributable to registry data, these findings are important, and warrant further research on how to improve limb salvage in different demographic settings.

International Consortium of Vascular Registries Consensus Recommendations for Peripheral Revascularisation Registry Data Collection.

OBJECTIVE/BACKGROUND: To achieve consensus on the minimum core data set for evaluation of peripheral arterial revascularisation outcomes and enable collaboration among international registries. METHODS: A modified Delphi approach was used to achieve consensus among international vascular surgeons and registry members of the International Consortium of Vascular Registries (ICVR). Variables, including definitions, from registries covering open and endovascular surgery, representing 14 countries in ICVR, were collected and analysed to define a minimum core data set and to develop an optimum data set for registries. Up to three different levels of variable specification were suggested to allow inclusion of registries with simpler versus more complex data capture, while still allowing for data aggregation based on harmonised core definitions. RESULTS: Among 31 invited experts, 25 completed five Delphi rounds via internet exchange and face to face discussions. In total, 187 different items from the various registry data forms were identified for potential inclusion in the recommended data set. Ultimately, 79 items were recommended for inclusion in minimum core data sets, including 65 items in the level 1 data set, and an additional 14 items in the more specific level 2 and 3 recommended data sets. Data elements were broadly divided into (i) patient characteristics; (ii) comorbidities; (iii) current medications; (iv) lesion treated; (v) procedure; (vi) bypass; (vii) endarterectomy (viii) catheter based intervention; (ix) complications; and (x) follow up. CONCLUSION: A modified Delphi study allowed 25 international vascular registry experts to achieve a consensus recommendation for a minimum core data set and an optimum data set for peripheral arterial revascularisation registries. Continued global harmonisation of registry infrastructure and definition of items will overcome limitations related to single country investigations and enhance the development of real world evidence.

Cardiovascular outcomes in patients with peripheral arterial disease as an initial or subsequent manifestation of atherosclerotic disease: Results from a Swedish nationwide study.

OBJECTIVE: Long-term progression of peripheral arterial disease (PAD) as initial manifestation of atherosclerotic arterial disease is not well described. Cardiovascular (CV) risk was examined in different PAD populations diagnosed in a hospital setting in Sweden. METHODS: Data for this retrospective cohort study were retrieved by linking data on morbidity, medication use, and mortality from Swedish national registries. Primary CV outcome was a composite of myocardial infarction, ischemic stroke (IS), and CV death. Kaplan-Meier analysis and Cox proportional hazards modeling was used for describing risk and relative risk. RESULTS: Of 66,189 patients with an incident PAD diagnosis (2006-2013), 40,136 had primary PAD, 16,786 had PAD + coronary heart disease (CHD), 5803 had PAD + IS, and 3464 had PAD + IS + CHD. One-year cumulative incidence rates of major CV events for the groups were 12%, 21%, 29%, and 34%, respectively. Corresponding numbers for 1-year all-cause death were 16%, 22%, 33%, and 35%. Compared with the primary PAD population, the relative risk increase for CV events was highest in patients with PAD + IS + CHD (hazard ratio [HR], 2.01), followed by PAD + IS (HR, 1.87) and PAD + CHD (HR, 1.42). Despite being younger, the primary PAD population was less intensively treated with secondary preventive drug therapy. CONCLUSIONS: PAD as initial manifestation of atherosclerotic disease diagnosed in a hospital-based setting conferred a high risk: one in eight patients experienced a major CV event and one in six patients died within 1 year. Despite younger age and substantial risk of future major CV events, patients with primary PAD received less intensive secondary preventive drug therapy.

Contemporary cardiovascular risk and secondary preventive drug treatment patterns in peripheral artery disease patients undergoing revascularization.

OBJECTIVE: Peripheral artery disease (PAD) is common worldwide, and PAD patients are increasingly offered lower limb revascularization procedures. The aim of this population-based study was to describe the current risk for cardiovascular (CV) events and mortality and also to elucidate the current pharmacologic treatment patterns in revascularized lower limb PAD patients. METHODS: This observational, retrospective cohort study analyzed prospectively collected linked data retrieved from mandatory Swedish national health care registries. The Swedish National Registry for Vascular Surgery database was used to identify revascularized PAD patients. Current risk for CV events and death was analyzed, as were prescribed drugs aimed for secondary prevention. A Cox proportional hazard regression model was used to explore risk factors for suffering a CV event. RESULTS: Between May 2008 and December 2013, there were 18,742 revascularized PAD patients identified. Mean age was 70.0 years among patients with intermittent claudication (IC; n = 6959) and 76.8 years among patients with critical limb ischemia (CLI; n = 11,783). Antiplatelet therapy, statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and beta-blockers were used by 73%, 60%, 57%, and 49% at admission for revascularization. CV event rate (a composite of myocardial infarction, ischemic stroke, or CV death) at 12, 24, and 36 months was 5.1% (95% confidence interval [CI], 4.5-5.6), 9.5% (95% CI, 8.7-10.3), and 13.8% (95% CI, 12.8-14.8) in patients with IC and 16.8% (95% CI, 16.1-17.6), 25.9% (95% CI, 25.0-26.8), and 34.3% (95% CI, 33.2-35.4) in patients with CLI. Best medical treatment, defined as any antiplatelet or anticoagulant therapy along with statin treatment, was offered to 65% of IC patients and 45% of CLI patients with little change during the study period. Statin therapy was associated with reduced CV events (hazard ratio, 0.76; 95% CI, 0.71-0.81; P < .001), whereas treatment with low-dose aspirin was not. CONCLUSIONS: Revascularized PAD patients are still at a high risk for CV events without a declining time trend. A large proportion of both IC and CLI patients were not offered best medical treatment. The most commonly used agent was aspirin, which was not associated with CV event reduction. This study calls for improved medical management and highlights an important and partly unmet medical need among revascularized PAD patients.

RSAD2 is abundant in atherosclerotic plaques and promotes interferon-induced CXCR3-chemokines in human smooth muscle cells.

In atherosclerotic lesions, monocyte-derived macrophages are major source of interferon gamma (IFN-γ), a pleotropic cytokine known to regulate the expression of numerous genes, including the antiviral gene RSAD2. While RSAD2 was reported to be expressed in endothelial cells of human carotid lesions, its significance for the development of atherosclerosis remains utterly unknown. Here, we harnessed publicly available human carotid atherosclerotic data to explore RSAD2 in lesions and employed siRNA-mediated gene-knockdown to investigate its function in IFN-γ-stimulated human aortic smooth muscle cells (hAoSMCs). Silencing RSAD2 in IFN-γ-stimulated hAoSMCs resulted in reduced expression and secretion of key CXCR3-chemokines, CXCL9, CXCL10, and CXCL11. Conditioned medium from RSAD2-deficient hAoSMCs exhibited diminished monocyte attraction in vitro compared to conditioned medium from control cells. Furthermore, RSAD2 transcript was elevated in carotid lesions where it was expressed by several different cell types, including endothelial cells, macrophages and smooth muscle cells. Interestingly, RSAD2 displayed significant correlations with CXCL10 (r = 0.45, p = 0.010) and CXCL11 (r = 0.53, p = 0.002) in human carotid lesions. Combining our findings, we uncover a novel role for RSAD2 in hAoSMCs, which could potentially contribute to monocyte recruitment in the context of atherosclerosis.

Effectiveness of supervised exercise, home-based exercise, or walk advice strategies on walking performance and muscle endurance in patients with intermittent claudication (SUNFIT trial): a randomized clinical trial.

AIMS: Supervised exercise is a guideline-recommended treatment in intermittent claudication (IC). Hospital-based supervised exercise programmes (SEPs) are underutilized, while home-based structured exercise programmes (HSEPs) have attracted interest. The results from HSEP in IC are inconsistent and may confer no benefit over walk advice (WA) and be less effective than SEP. The aim of the study was to compare the effectiveness of best medical treatment, including Nordic pole WA alone, or WA + SEP or WA + HSEP for patients with IC. METHODS AND RESULTS: This three-armed, multicentre randomized clinical trial enrolled patients with IC; all patients received best medical treatment including walking poles and the advice of regular Nordic pole walking (WA). For HSEP and SEP, additional exercise programmes were provided. The primarily investigated hypothesis was a non-inferiority analysis of SEP vs. HSEP regarding the 6-min walk test (6MWT) maximum distance, with a pre-defined non-inferiority margin of 50 m. Supporting outcomes included muscle endurance tests and the walking impairment questionnaire. Outcomes were assessed at baseline, 3, 6, and 12 months by a blinded evaluator. Altogether 166 patients (mean age 72 years; 59% males) were randomized. In HSEP and SEP, 24 and 26% patients, respectively, were fully exercise adherent. All three groups improved pain-free walking distance over time, but there were no significant intergroup differences. The intergroup 6MWT difference between SEP and HSEP from 0 to 12 months was -11.6 m, 95% confidence interval: -36.4 to 13.0 m (i.e. within the pre-specified non-inferiority margin). CONCLUSION: The HSEP was non-inferior to SEP in patients with IC. There were no significant differences observed between the three groups at 1 year. REGISTRATION: ClinicialTrials.gov: NCT02341716.

Presence of asymptomatic Peripheral Arterial Disease in combination with common risk factors elevates the cardiovascular risk Substantially.

Background and aims: This study evaluates the risks for adverse cardiovascular (CV) events in Asymptomatic Peripheral Arterial Disease (APAD) combined with different traditional CV risk factors. Methods: A population-based observational study of 8000 subjects, identified 559 subjects as having APAD through ankle-brachial index (ABI) measurements and questionnaires regarding limb symptoms. This cohort and subgroups classified by presence of different traditional CV risk factors at baseline were assessed for 10 years on CV outcome. The recorded endpoints were all-cause mortality, CV mortality and non-fatal CV events. Results: Before subdividing the APAD subjects, the CV mortality incidence was 28.5 deaths per 1000 person-years as compared to 8.7 deaths for references without APAD. For subjects with hypertension at baseline the CV mortality incidence was 35.4 when combined with APAD and 11.7 without. In women with hypertension but without other risk factors, presence of APAD increased the age-adjusted Hazard Ratio (HR) for fatal and non-fatal CV events by 1.86 [CI 1.54,2.24, p < 0.001]. Conclusions: ABI measurements should be considered an important indication for aggressive multifactorial risk factor reduction in populations with any other prevalent CV risk factor. In hypertension, diabetes mellitus and a smoking history, coexisting APAD contributes significantly to the increased age-adjusted CV risk.

Differences in presentation of symptoms between women and men with intermittent claudication.

BACKGROUND: More women than men have PAD with exception for the stage intermittent claudication (IC). The purpose of this study was to evaluate differences in disease characteristics between men and women when using current diagnostic criteria for making the diagnosis IC, defined as ABI < 0.9 and walking problems. STUDY DESIGN: Cohort study METHODS: 5040 elderly (median age 71) subjects participated in a point-prevalence study 2004. They had their ABI measured and filled out questionnaires covering medical history, current medication, PAD symptoms and walking ability. The prevalence of IC was 6.5% for women and 7.2% for men (P = 0.09). A subset of subjects with IC (N = 56) was followed up four years later with the same procedures. They also performed additional tests aiming to determine all factors influencing walking ability. RESULTS: Men with IC had more concomitant cardiovascular disease and a more profound smoking history than women. Women, on the other hand, reported a lower walking speed (P < 0.01) and more joint problems (P = 0.018). In the follow up cohort ABI, walking ability and amount of atherosclerosis were similar among the sexes, but women more often reported atypical IC symptoms. CONCLUSION: Sex differences in the description of IC symptoms may influence diagnosis even if objective features of PAD are similar. This may influence accuracy of prevalence estimates and selection to treatment.