Peripheral Artery Disease Cohort Research Articles

Assessment of Frailty Among Older Adults in the Physical Activity Daily Trial.

Frailty is common among cardiac patients; however, frailty assessment data from patients with peripheral arterial disease (PAD) are limited. The purpose of this observational study was to identify the prevalence and factors related to frailty in addition to unique frailty marker groupings in a cohort of sedentary adults with PAD. We grouped three PAD-relevant frailty characteristics using Fried's frailty phenotype -1) exhaustion, (2) weakness, and (3) slowness-and observed the prevalence of pre-frailty (1-2 characteristics) and frailty (3 characteristics) in the PAD cohort. Of the 106 participants, 34.9% were robust/non-frail, 53.8% were pre-frail, and 2.8% were frail. Exhaustion (33.3%) was the most occurring characteristic followed by weakness (20.0%) and slowness (5.0%). The grouping of weakness + slowness (10.0%) was the most prevalent followed by exhaustion + weakness (8.3%) and exhaustion + slowness (5.0%). Among pre-frail participants, ankle brachial index was correlated with a reduction in gait speed.

Peripheral artery disease and extracorporeal membrane oxygenation: Examining a high-risk cohort over time.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a resource-intensive approach for the management of refractory cardiogenic shock. Within this population exists a substantial cohort of patients with peripheral artery disease (PAD), which independently increases the risk of complications and all-cause mortality. We studied 10-year national trends of the impact of PAD among VA-ECMO recipients to better understand the prevalence of PAD and implications on outcomes in this vulnerable population. This 10-year retrospective, propensity score-matched study identified all adult patients (≥18) who underwent VA-ECMO between 2009 and 2018, from a large US database (National Inpatient Sample). Patients with an ICD diagnosis of PAD were identified. The primary endpoints of in-hospital mortality, bleeding complications and major limb loss (above- or below-knee amputation) were compared between patients with PAD to those without. A total of 6768 patients were identified, of which 342 (5.3%) had PAD. The median age at admission was significantly higher in PAD patients [64years vs. 55years; p < .01], as was male gender [71% vs. 64%; p < .01]. Patients with PAD had higher rates of smoking (38.9% vs. 23.3%), hypertension (71.1% vs. 50%), diabetes (37.4% vs. 27.0%), chronic kidney disease (30.1% vs. 18.0%), coronary artery disease (76.0% vs. 35.0%) and dyslipidemia (76.0% vs. 35.0); all p < .01. After propensity-matching 2:1 for comorbidities, PAD patients were found to have significantly greater overall complications, including in-hospital mortality, bleeding, surgical wound infections, pseudoaneurysms, and major adverse limb events [71.9% vs. 63.9%; p < .01]. Subgroup analysis revealed greater in-hospital mortality [62.2% vs. 55.3%; p < .05], major amputations [4.1% vs. 0.3%; p < .01] and blood transfusions [32.2% vs. 26.2%; p < .05] in PAD patients. Over 2014-2018, the non-PAD group demonstrated statistically discernable trends in a 51.1% decrease in overall complications and a 28.1% increase in survival to discharge (all p < .01). Over the same time period the PAD cohort experienced a modest, nonsignificant, decrease in complications [7.0%, p = .40] and a decrease in those surviving to discharge [47.1% vs. 40.5%, p = .91]. Patients with PAD on VA-ECMO are sicker at baseline and experience significantly greater major amputations and higher in-hospital mortality. They have not benefitted from the considerable decrease in complication rates and increase in survival to discharge over time as compared to their non-PAD counterparts. These findings demonstrate the substantial frailty of the PAD population within an already high-risk cohort, and highlight the need for better procedural approaches and innovative technologies.

Long-Term Outcomes in Patients With Peripheral Arterial Disease Who Undergo Free Flap Reconstruction for Chronic Lower Extremity Wounds.

Free tissue transfer (FTT) is critical for limb salvage of chronic lower extremity (LE) wounds. In patients with peripheral arterial disease (PAD), FTT LE reconstruction can be challenging due to limited vessel selection for anastomosis. The study aims to evaluate our surgical and functional outcomes after FTT to LE in patients with PAD. A retrospective review identified patients who underwent LE free flap reconstruction between 2011 and 2021. All patients underwent preoperative arteriogram and subsequent FTT. Patients were classified into PAD or non-PAD cohorts, based on the presence of LE arterial stenoses or occlusions identified on arteriogram. Primary outcomes included complications, flap success, need for post-FTT vascular reintervention, limb salvage, and ambulatory status. A total of 253 patients underwent FTT to LE, with 84 patients (33.2%) in the PAD cohort. Patients with PAD had a higher prevalence of diabetes (83.3% vs 39.1%, P < 0.001) and end-stage renal disease (8.3% vs 2.4%, P = 0.028). Osteomyelitis was more common in the PAD group (73.8% vs 55.0%, P = 0.004). Free tissue transfer donor sites and flap composition were similar between cohorts. At a mean follow-up of 21.1 months, limb salvage rates were similar between non-PAD and PAD cohorts (90.5% vs 84.5%, P = 0.158), with no significant differences in ambulatory status or mortality. Higher complication rates occurred in the PAD cohort (38.1% vs 20.7%, P = 0.003), of which partial flap necrosis was more prevalent in the PAD group (6.0% vs 0.6%, P = 0.016). There was no difference in flap success rates between groups (P = 0.430). More postflap angiograms were performed in the PAD group (29.8% vs 7.1%, P < 0.001), with repeat percutaneous endovascular intervention performed in 68.0% of the PAD group versus 33.3% of the non-PAD group (P < 0.001). This is the largest study to demonstrate excellent long-term limb salvage outcomes in patients with PAD who undergo FTT to LE. Percutaneous endovascular intervention and FTT are effective methods to achieve limb salvage in vasculopathic patients with chronic LE wounds.

The prognostic capability of inflammatory proteins in predicting peripheral artery disease related adverse events.

Levels of inflammatory proteins and their prognostic potential have been inadequately studied in patients with peripheral artery disease (PAD). In this study, we quantified and assessed the ability of inflammatory proteins in predicting PAD-related adverse events. In this prospective case-control study, blood samples were collected from patients without PAD (n = 202) and patients with PAD (n = 275). The PAD cohort was stratified by disease severity based on ankle brachial index (ABI): mild (n = 49), moderate (n = 164), and severe (n = 62). Patients were followed for 2 years. Plasma concentrations of 5 inflammatory proteins were measured: Alpha-2-Macroglobulin (A2M), Fetuin A, Alpha-1-Acid Glycoprotein (AGP), Serum Amyloid P component (SAP), and Adipsin. The primary outcome of our study was major adverse limb event (MALE), defined as the need for vascular intervention (open or endovascular revascularization) or major amputation. The secondary outcome was worsening PAD status, defined as a drop in ABI greater than or equal to 0.15 over the study period. Multivariable logistic regression was performed to assess the prognostic value of inflammatory proteins in predicting MALE, adjusting for confounding variables. Compared to patients without PAD, three inflammatory proteins were differentially expressed in patients with PAD (AGP, Fetuin A, and SAP). The primary outcome (MALE) and secondary outcome (worsening PAD) status were noted in 69 (25%) and 60 (22%) patients, respectively. PAD-related adverse events occurred more frequently in severe PAD patients. Based on our data, the inflammatory protein AGP was the most reliable predictor of primary and secondary outcomes. On multivariable analysis, there was a significant association between AGP and MALE in all PAD disease states [mild: adjusted HR 1.13 (95% CI 1.05-1.47), moderate: adjusted HR 1.23 (95% CI 1.16-1.73), severe: adjusted HR 1.37 (95% CI 1.25-1.85)]. High levels of AGP were associated with lower 2-year MALE-free survival in all PAD disease states [mild (64% vs. 100%, p = 0.02), moderate (64% vs. 85%, p = 0.02), severe (55% vs. 88%, p = 0.02), all PAD (62% vs. 88%, p = 0.01)]. Levels of inflammatory protein AGP may help in risk stratifying PAD patients at high risk of MALE and worsening PAD status and subsequently facilitate further vascular evaluation and initiation of aggressive medical/surgical management.

Health status and cognitive function for risk stratification in chronic coronary and peripheral artery disease.

It is unclear whether health status and cognitive function assessments can augment traditional coronary artery disease (CAD) and peripheral artery disease (PAD) biomedical risk prediction frameworks. We examined the association between health status and cognitive function and subsequent adverse cardiovascular and limb events in CAD and PAD. Stable CAD and PAD patients from the international, multi-centre COMPASS trial completed the visual analogue scale (VAS) of the EQ-5D-3L to assess overall health status, and the Digit Symbol Substitution test (DSST) to assess cognitive function. Main outcomes were incident development of major adverse cardiovascular events, and the combined endpoint major adverse cardiovascular or limb events. The EQ VAS (per 10 unit increase) and DSST (per 5 unit increase) were added to fully adjusted (medications, demographics, cardiovascular history and risk factors) hierarchical Cox regression models. A total of 23 433 patients were in the CAD cohort and 6899 in the PAD cohort. Among both the CAD and PAD groups, higher scores on the EQ VAS (CAD: HR = 0.89, 95%CI 0.88-0.89; PAD HR = 0.89, 95%CI 0.88-0.89) and DSST (CAD HR = 0.95, 95%CI 0.94-0.95) (PAD HR = 0.95, 95%CI 0.94-0.95) were associated with a lower risk of a major adverse cardiovascular or limb events. Population attributable risks associated with the lower two quartiles vs. upper quartiles for the EQ-5D and DSST scores were 7% and 16%, respectively in the CAD cohort; and for PAD, at 14% and 18%, respectively. Adding health status and cognitive functioning information to biomedical evaluations can augment cardiovascular risk-stratification in CAD and PAD. NCT01776424.

DIETARY INTAKE AND CARDIOVASCULAR OUTCOMES IN PATIENTS WITH CHRONIC VASCULAR DISEASE IN THE COMPASS TRIAL

DIETARY INTAKE AND CARDIOVASCULAR OUTCOMES IN PATIENTS WITH CHRONIC VASCULAR DISEASE IN THE COMPASS TRIAL

Abstract P128: Prevalence Of Pre-frailty And Frailty In The Physical Activity Daily (PAD) Trial

Introduction: Frailty is a multidimensional, geriatric syndrome characterized by decreased physiologic reserve and resistance to stressors. Frailty is associated with increased mortality among cardiac patients; however, data on patients with peripheral arterial disease (PAD) are limited. Purpose: The purpose of this observational study was to identify the prevalence of unique physical frailty clusters in a sedentary, PAD cohort in the Physical Activity Daily (PAD) Trial. Methods: This study utilized baseline information from the Physical Activity Daily (PAD) Trial (2014 – 2021). Sedentary adults with documented PAD, defined as ankle-brachial index [ABI] &lt; 0.9, within the University of Michigan and University of Alabama at Birmingham health systems were enrolled. We clustered three PAD-relevant frailty phenotypes using the Fried’s frailty index —1) self-reported exhaustion (SRE), 2) weakness (WN), and 3) slow walking speed (SWS)—and observed the prevalence of pre-frailty (1-2 characteristics) and frailty (3 characteristics) in the PAD cohort. Results: A total of 106 participants (age, 66.9 [8.4] years; female 37 [34.9%]; White 89 [84.8%]) were assessed for unique frailty clusters. Of the 106, 34.9% were characterized as robust/non-frail, 61.3% were pre-frail and 3.7% were frail. Overall, the most common phenotype component among this PAD cohort was WN (44.3%). Among pre-frail and frail participants, WN (30.4%) was the single-most occurring phenotype followed by SRE (23.2%) and SWS (5.8%). Additionally, WN + SWS (18.9%) was the most prevalent pre-frailty cluster followed by SRE + WN (13.0%) and SRE + SWS (2.9%). Conclusions: In this cohort of participants with PAD, pre-frailty was the most common accounting for 61.3%. Given the high number of adults who transition from pre-frailty to frailty, efforts to identify the clustering of phenotypes in PAD patients who are pre-frail is warranted. The implementation of rehabilitative strategies within this population is of importance to prevent the development of pre-frailty into frailty.

Impact of peripheral artery disease on prognosis after percutaneous coronary intervention: Outcomes from the multicenter prospective e-ULTIMASTER registry

Background and aimsPatients with peripheral artery disease (PAD) represent a high risk group, and have an increased risk of cardiovascular events and worse cardiovascular outcomes. Our aim was to study the impact of PAD among patients undergoing percutaneous coronary intervention (PCI) with a newer-generation thin-strut DES. MethodsIn this analysis of the e‐ULTIMASTER registry, patients with and without known PAD undergoing PCI were compared. A propensity-score was used to adjust for differences between the groups. The primary outcome was target lesion failure (TLF): a composite of cardiac death, target‐vessel related myocardial infarction, and/or clinically driven target lesion revascularization at 1‐year follow‐up. ResultsOf 33,880 patients included in the analysis, PAD was present in 2255 (6.7%). Patients with PAD were older (69.0 ± 10.0 vs. 63.8 ± 11.3 years) with a higher burden of comorbidities. Patients with PAD were less likely to present with STEMI (9.6% vs. 21%), and more likely to undergo complex PCI (left main 5.5% vs. 3.0% ostial lesions 10.4% vs. 7.0%, bifurcations 14.5% vs. 12.3% and calcification 26.8% vs. 17.8%). PAD was found to be independently associated with 41% increased risk for TLF. The risk for all cause death and for cardiac death was 75% and 103% higher, respectably. No difference was found in the rates of stent thrombosis, clinically driven target lesion revascularization, or myocardial infarction (MI). ConclusionsPatients with PAD are at higher risk for (cardiac) death post PCI, but not target vessel or lesion repeat revascularizations. The PAD cohort represents a population with a higher risk clinical profile. Further research combining medical and device therapies is needed to further improve the outcomes in this high-risk population.

Atherothrombotic residual risk in coronary and peripheral artery disease patients on guideline-recommended antiplatelet monotherapy: baseline preliminary results from the RESRISK study

Abstract Introduction Greater recognition of a multi-factorial approach to risk factor control and use of guideline-recommended evidence-based therapies, including antiplatelets, have led to a decline in recurrent cardiovascular (CV) events among those with atherosclerotic CV disease (ASCVD). While residual risk still persists, recent evidence-based therapies have emerged which could further attenuate CV risk in these individuals, including novel drugs adjunct to antiplatelet therapies. Purpose The RESRISK study aims to quantify the residual atherothrombotic risk among a routine care cohort with ASCVD on guideline-recommended antiplatelet monotherapy (APMT). As a first step, we assessed the characteristics of participants at entry in the study, including risk factor burden, comorbidities and use of evidence-based medications. Methods A retrospective (2010–18) cohort of 758,325 patients with coronary (CAD) or peripheral artery disease (PAD) aged ≥18 years was derived from the UK Clinical Practice Research Datalink. Patients were selected if they were on recommended APMT according to ESC guidelines and NICE (aspirin for CAD; clopidogrel for PAD), were diagnosed with CAD/PAD prior to initiating APMT, and had ≥1 year of baseline data prior to index date (date of first APMT prescription). History of atrial fibrillation and haemorrhagic stroke led to exclusion. Results 174,210 patients with CAD (and no prior history of PAD) and 11,050 patients with PAD (and no prior history of CAD) met the inclusion criteria. Within the selection process for the PAD cohort, 51,114 patients were excluded due to being prescribed aspirin instead of clopidogrel. Baseline characteristics are shown in Table. Mean age was ∼70 years for both cohorts. While prevalence of hypertension was similar in both cohorts, presence of diabetes was 1.6 times higher in PAD patients. Stroke was 2.5 times more prevalent among PAD patients. The proportion of patients with systolic/diastolic blood pressure ≤130/≤85 mmHg were 41.6%/84.5% for CAD and 32.2%/80.6% for PAD (corresponding numbers for ≤140/≤90 mmHg were 67.8%/93.4% for CAD, and 58.8%/91.1% for PAD). Mean LDL-C was 2.4±0.9 and 2.6±1.1 mmol/L in CAD and PAD patients, with 10.7% and 9.5% of them, respectively, having an LDL-C &amp;lt;1.4 mmol/L (25.1% and 22.6% for LDL-C &amp;lt;1.8). Conclusions Among a contemporary cohort with ASCVD on guideline-recommended APMT, risk factor burden is high and attainment of guideline-recommended targets remains largely suboptimal. Prevalence of diabetes among PAD patients is particularly high. A large gap exists between guideline recommendations and guideline-recommended goal attainment. Greater attention to risk factor control and use of appropriate evidence-based therapy is required to reduce the potential risk of recurrent events among this high-risk population. Subsequent follow-up analysis with linkage to outcomes will provide quantification of the consequences of current practice on residual risk. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): All financial support for this research has been provided by Bayer plc. Table 1

Correlation of Patient Activation Measure Level with Patient Characteristics and Type of Vascular Disease

Patient activation or level of engagement in one's medical care is linked to hospital readmissions and worse outcomes in a number of diseases. Patients with higher levels of activation are typically guiding their care rather than acting as passive observers of care. This study aims to determine if either patient demographics or type of vascular disease can predict patient activation. All patients presenting over a 4-month period to an outpatient vascular clinic were asked to complete the Patient Activation Measure (PAM) survey. In total, 257 completed surveys were collected. Survey responses were scored on a Likert scale with anchors. Responses are tallied with a score of 1-100 and converted to summary levels 1-4 in accordance with the previously validated scoring system. Level 1 patients are considered disengaged and overwhelmed. Patients in level 2 are becoming aware of their health care, but still struggle. Level 3 patients are taking action, while level 4 represents patients who are maintaining healthy behaviors and pushing further. Chi-squared test and multivariable regression were then performed to determine if patient characteristics or type of disease correlated with activation levels. In total, 257 patients completed the survey. The mean participant age was 67years (±15). Sixteen percent of patients lived alone, 58% were married, and in 39% mean household income was <$50,000. Overall, 21 patients (8.2%) were classified as level 1, 65 (25%) level 2, 94 (37%) level 3, and 77 (30%) level 4. The group comprised 32% peripheral artery disease (PAD), 20% carotid, 18% aortic/aneurysm, 14% venous, and 16% were various other vascular diseases. Over each disease group there was a wide range of activation, but no significant difference between the type of vascular disease and activation level. Chronic limb-threatening ischemia (CLTI) patients comprised 35% (n=29) of the PAD group, and 66% of these patients reported an activation level of 3 (n=10) or 4 (n=9). There was no difference in the levels of activation reported by the CLTI patients compared to the general PAD cohort (P=0.99). Multivariable analysis demonstrated that age, level of education, household income, and type of vascular disease correlated with PAM score, but there was no correlation between length of symptoms, race, or gender. Patient activation is unpredictable using patient characteristics or type of vascular disease, and CLTI patients report high activation levels. Quality databases that collect only patient demographics may not fully capture patient predictors of poor outcomes. Use of the PAM survey should be further explored in vascular patients to correlate activation level with vascular-specific outcomes.

Usability of a Digital Registry to Promote Secondary Prevention for Peripheral Artery Disease Patients.

ObjectiveTo evaluate usability of a quality improvement tool that promotes guideline-based care for patients with peripheral arterial disease (PAD).Patients and MethodsThe study was conducted from July 19, 2018, to August 21, 2019. We compared the usability of a PAD cohort knowledge solution (CKS) with standard management supported by an electronic health record (EHR). Two scenarios were developed for usability evaluation; the first for the PAD-CKS while the second evaluated standard EHR workflow. Providers were asked to provide opinions about the PAD-CKS tool and to generate a System Usability Scale (SUS) score. Metrics analyzed included time required, number of mouse clicks, and number of keystrokes.ResultsUsability evaluations were completed by 11 providers. SUS for the PAD-CKS was excellent at 89.6. Time required to complete 21 tasks in the CKS was 4 minutes compared with 12 minutes for standard EHR workflow (median, P = .002). Completion of CKS tasks required 34 clicks compared with 148 clicks for the EHR (median, P = .002). Keystrokes for CKS task completion was 8 compared with 72 for EHR (median, P = .004). Providers indicated that overall they found the tool easy to use and the PAD mortality risk score useful.ConclusionsUsability evaluation of the PAD-CKS tool demonstrated time savings, a high SUS score, and a reduction of mouse clicks and keystrokes for task completion compared to standard workflow using the EHR. Provider feedback regarding the strengths and weaknesses also created opportunities for iterative improvement of the PAD-CKS tool.

Predictive power of novel and established obesity indices for outcome in PAD during a five-year follow-up

Background and aimsPrevious data show contradicting results regarding relevance of obesity on outcome in peripheral arterial disease (PAD). Thus, this study aims to evaluate the predictive power of obesity as measured by established and novel obesity indices (waist circumference WC, waist-hip ratio WHR, body-mass index BMI, body adiposity index BAI, visceral adiposity index VAI, weight-adjusted waist index WWI) in a PAD cohort. Methods and resultsIn 367 patients with diagnosed PAD anthropometric parameters were assessed at study inclusion in an observational study. Mortality data was retrieved from the central death registry after five years. Outcome analyses were performed by multivariable Cox-regression models. 57 PAD patients (15.5%) died during the follow-up, of those 36 were categorized as cardiovascular origin. Patients from the all-cause mortality group were older, more often diabetics with a worse glucose control and had worse renal function. Obesity indices were not significantly different between the event and control group. None of the evaluated risk factors predicted cardiovascular or all-cause death after multivariable adjustment for age, gender, LDL-C, serum creatinine, systolic blood pressure, CRP, smoking habits, diabetes status and previous history of peripheral revascularisation (all-cause WC 1.007 (0.983–1.031), WHR 1.772 (0.106–29.595), BMI 1.006 (0.939–1.078), BAI 1.002 (0.945–1.063), VAI 1.019 (0.895–1.161), WWI 1.085 (0.831–1.416); cv-death WC 1.007 (0.978–1.036), WHR 0.382 (0.006–25.338), BMI 1.004 (0.918–1.098), BAI 1.034 (0.959–1.116), VAI 1.036 (0.885–1.213), WWI 1.061 (0.782–1.441)). ConclusionObesity as risk marker estimated by indices both for general and visceral adiposity, does not predict mortality in a secondary prevention cohort of PAD patients.

Searching for a Common Thrombo-Inflammatory Basis in Patients With Deep Vein Thrombosis or Peripheral Artery Disease.

Background: Inflammation and hypercoagulability play a pivotal role in venous thromboembolism and atherothrombosis. Since venous thrombosis increases the risk of atherothrombotic events and vice versa, common mechanisms may be involved.Objectives: To elucidate the role of neutrophils and coagulation in the occurrence of atherothrombotic events in patients with a history of deep vein thrombosis (DVT or peripheral artery disease (PAD).Materials and Methods: We studied 115 patients from two cohorts (75 DVT, 40 PAD). From those with PAD, 20 patients had progressive disease; from those with DVT, 25 patients had a recurrent DVT and 25 suffered from post thrombotic syndrome (PTS); patients were age and sex matched to DVT and PAD patients without events. Markers of neutrophil recruitment (p-selectin) and activation [nucleosomes, human neutrophil elastase- α1anti-trypsin (HNE-AT)], an anti-inflammatory marker (Lipoxin A4) and a clotting activity marker (d-dimer), were measured with ELISA. Coagulation potential was analyzed by thrombin generation (CAT method).Results: Higher nucleosome levels were found in DVT patients [11.3 U/mL (7.4–17.7)] compared to PAD patients [7.1 U/mL (5.1–13.8)], lower HNE-AT levels were found in DVT patients [33.4 ng/mL (23.5–40.5)] in comparison to PAD patients [158 ng/mL (88.1–283)]. No difference in nucleosome levels was found between DVT patients with cardiovascular (CV) events [12.6 U/mL (8.2–16.1)], and PAD patients with CV events [6.9 U/mL (4.9–11.2)]. Lipoxin A4 levels appeared to be significantly lower in DVT [2.4 ng/mL (1.7–4.8)] vs. PAD [35.6 ng/mL (16.6–80.1)], with similar results in DVT patients with CV events vs. PAD patients with CV events. Thrombin generation showed higher ETP [160.4% (141.1–215.4)], and peak height [292.1% (177.9–330)] values in DVT patients. D-dimer levels were significantly lower in the DVT cohort [330 ng/mL (220–550)] compared to the PAD cohort [550 ng/mL (369–959)].Conclusion: In DVT patients, neutrophil activity does not appear to be an important driver of CV events. Although neutrophil activity is more pronounced in PAD, its effect is partly dampened by Lipoxin A4. Moreover, no associations were found between NET products and coagulation activity, suggesting that neutrophil activation does not play a pivotal role in the risk of thrombosis in either DVT or PAD.

Angiopoietin-2 and Survival in Peripheral Artery Disease Patients

Survival of peripheral arterial disease (PAD) patients increased over the last decade due to increased use of secondary preventive medication and rapid revascularization of PAD patients. Angiogenetic markers such as vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2) and its receptor Tie-2 might be useful markers to assess the residual risk for mortality in PAD patients. The aim of this study was to evaluate angiogenetic markers for the prediction of mortality in a PAD cohort. For this purpose, 366 patients (mean age: 69 ± 10 years) with PAD Fontaine stage I or II were included and followed up over a 5-year study period. Serum Ang-2, Tie-2 and VEGF levels were measured by bead-based multiplex assay. All-cause mortality and major cardiovascular events (MACE) including all-cause death, non-fatal stroke and non-fatal myocardial infarction were analysed by Kaplan-Meier and Cox regression analyses after 5 years. Ang-2 was associated with Tie-2 (R = 0.151, p = 0.006) and VEGF levels (R = 0.160, p = 0.002). However, only Ang-2 was linked to all all-cause mortality in PAD patients (hazard ratio [HR]: 1.55 [1.23-2.15], p = 0.008) even after adjustment for age and gender, haemoglobin A1c, low-density lipoprotein cholesterol, systolic blood pressure and glomerular filtration rate (HR: 1.44 [1.03-2.00], p = 0.032). Furthermore, an association of Ang-2 and MACE in PAD patients (HR: 1.36 (1.03-1.78), p = 0.028) was found. This result implies that Ang-2 might be used as an additional marker to stratify PAD patients to predict poor mid-term life expectancy.

Cardiovascular risk reduction in referrals to outpatient vascular clinics

Introduction Patients with peripheral arterial disease (PAD), aneurysmal disease (AD) or carotid atherosclerosis are at high cardiovascular risk, necessitating secondary cardiovascular protection. The aim of this study was to determine compliance with cardiovascular risk reduction guidelines in new patients referred to vascular clinics. Methods A multicentre collaborative national observational audit of new patients referred to eight tertiary general vascular clinics over a three-month period in England and Wales was conducted by the Vascular and Endovascular Research Network (VERN). Referral letters, case notes and investigations were reviewed by local investigators, and data analysed by VERN. Results A total of 656 patients were included in the study: 73.2% had PAD, 23.2% had AD and 3.7% had carotid atherosclerosis. A third (37.5%) were current smokers, two-thirds (61.7%) were on antiplatelet therapy and two-thirds (61.5%) were on statin therapy. Smoking was more prevalent in the PAD cohort (PAD 41.4%, AD 27.5%, p=0.003). However, more PAD patients were on antiplatelet therapy (PAD 63.9%, AD 53.3%, p=0.024). Both antiplatelet and statin prescription significantly increased with the number of cardiovascular risk factors. Patients with a previous cardiac or cerebrovascular history were more likely to have stopped smoking, and to be on antiplatelet and statin therapy (p&lt;0.0001 for each). Overall, 47.3% of patients were on both antiplatelet and statin therapy, and 28.9% were on antiplatelet and statin therapy and not smoking. Conclusions This study highlights deficiencies in cardiovascular risk minimisation in patients with established vascular disease. Patients with concomitant cardiac or cerebrovascular disease were more likely to be on best medical therapy.

Sarcopenia in Peripheral Arterial Disease: Prevalence and Effect on Functional Status

Objectives(1) To determine the prevalence of sarcopenia in older men with peripheral arterial disease (PAD); (2) to compare a subgroup of the group with age-, race-, sex-, and body mass index (BMI)–matched non-PAD control counterparts, and (3) to compare the functional status of those with PAD with and without sarcopenia. DesignCohort study. SettingMedical center. ParticipantsSedentary community-dwelling men (N=108; age, >50y) with a confirmed diagnosis of PAD (44% blacks; BMI, 27.8±0.4kg/m2; ankle-brachial index, .62±.01). InterventionsNot applicable. Main Outcome MeasuresDual-energy x-ray absorptiometry scans were used to assess appendicular lean mass and determine the prevalence of sarcopenia by/height2. Treadmill tests were used to determine claudication onset time, peak walking time, and claudication recovery time. 6-Minute walk distance was also measured. ResultsSarcopenia prevalence in our PAD cohort was 25%. The PAD subgroup (n=42) matched with control counterparts in terms of race, sex, age, and BMI had higher prevalence rates than did their non-PAD counterparts (23.8% vs 2.4%; P<.05). Individuals with sarcopenia (n=28) had a shorter 6-minute walk distance (326±18.8m vs 380±9.7m; P<.05) and higher claudication recovery time (592±98s vs 395±29s; P<.05) than did individuals with PAD but without sarcopenia (n=80). There was no difference in claudication onset time or peak walking time between the PAD groups. ConclusionsMen with PAD demonstrate a high prevalence of sarcopenia. Those with sarcopenia and PAD demonstrate decreased mobility function.

Abstract 008: Statin Use and Its Facility Level Variation in Patients With Peripheral Artery Disease: Insights From the Department of Veterans Affairs

Background: The 2013 ACC/AHA cholesterol guideline recommends high-intensity statin therapy in patients 75 years or younger and moderate-intensity statin therapy in patients &gt; 75 years with atherosclerotic cardiovascular disease including those with peripheral artery disease (PAD). Statin prescribing patterns and their facility-level variation in patients with PAD are unknown. Methods: We examined the frequency and facility-level variation in the use of any and correct intensity of statins in patients with known PAD receiving primary care in 130 facilities across the Veterans Affairs (VA) health care system with or without concomitant ischemic heart disease (IHD) or ischemic cerebrovascular disease (ICVD). We calculated the median rate ratios (MRR) adjusted for patient demographic factors to assess the magnitude of facility-level variation in statin prescribing patterns for comparable patients. Results: Among 194,151 patients with PAD, 88,905 (45.8%) had PAD without IHD (with or without ICVD) and 70,404 (36.3%) had PAD without IHD or ICVD. Rates of statin use in the entire PAD cohort, patients with PAD without IHD and PAD alone were 79.0%, 69.1% and 66.3%, respectively. Median facility-level rates of statin use were 78.9% (IQR 75.9-81.5), 69.2% (65.4-72.6) and 66.4% (62.6-70.1), respectively. Correct intensity statins were prescribed among 40.9% for the entire PAD cohort, 28.9% of those with PAD without IHD, and 26.4% of those with PAD alone. Median facility-level rate of correct statin intensity use in all PAD patients was 40.1% (36.4-44.2), 27.8% (24.1-32.4) for patients with PAD without IHD and 25.3% (10.8-29.7) in patients with PAD alone. Calculated MRRs reflected a 20-22% variation among two facilities in treating identical PAD patients with statin therapy and a 24-28% variation in treating identical patients with correct statin intensity (Table). Conclusions: The use of statin and especially correct statin intensity is suboptimal in PAD patients, especially in PAD patients without concomitant IHD or ICVD. There is a significant facility-level variation in the receipt of guideline directed statin therapy in PAD patients. Interventions are needed to improve guideline directed moderate to high-intensity statin use and to reduce variation in care in this high-risk group.

Supervised exercise therapy in the management of peripheral arterial disease - an assessment of compliance.

Supervised exercise therapy (SET) is an effective option in the management of peripheral arterial disease (PAD). Unfortunately, poor compliance remains prevalent. This study aimed to assess patient exercise compliance and to identify factors influencing symptomatic improvement and SET participation. Data regarding attendance at SET for this cohort study were extracted from a prospectively maintained database of patients with claudication attending SET at Dublin City University. All patients had ankle brachial index confirmed PAD with associated intermittent claudication. Exercise performance and symptomatic data were gathered retrospectively using patient charts and interviews. Ninety-eight patients were referred for SET during the study period. The mean age was 69.2 (± 10.1) with 18 % being female. Median follow-up was 25.1 months (IQ range 17.0-31.6). Overall, the mean number of sessions attended per patient was 19.5. Exercise compliance was associated with a significant improvement in symptoms (p = 0.001). Other factors including anatomical level of claudication (P = 0.042) and educational level (p = 0.007) were found to affect the outcome of SET. Multivariate analysis revealed hypertension as a predictor of symptomatic outcome after SET (p = 0.045). Furthermore, ex-smokers (p = 0.021) and those previously diagnosed with hypercholesterolaemia (p = 0.020) or ischaemic heart disease (p = 0.029) had superior exercise compliance. Using linear regression, smoking history (p = 0.024) was identified as a predictor of compliance to SET. Establishing exercise compliance remains challenging in the PAD cohort. Pre-exercise patient education and personalised exercise prescriptions may result in improvements in function and compliance.

The Impact of Chronic Kidney Disease on Hospitalized Patients With Peripheral Arterial Disease and Critical Limb Ischemia.

Peripheral arterial disease (PAD) and chronic kidney disease (CKD) are major public health problems worldwide. Evaluations of large-scale data on morbidity, outcome, and costs in patients having PAD with CKD are essential. Cross-sectional nationwide population-based analysis of all hospitalizations for PAD during 2009 in Germany focused on the stage-related impact of CKD on morbidity, in-hospital mortality, amputations, length of hospital stay, and health-related expenditure. The total number of hospitalizations was 483 961. Of those, 132 993 (27.5%) had CKD. Chronic kidney disease caused 1.8-fold higher amputation rate ( P < .001) with a stepwise increasing rate with higher CKD stage. Chronic kidney disease doubled in-hospital mortality of patients with PAD (7.8%; n = 10 421) versus 4.0% (n = 14 174, P < .001) with a stepwise increasing risk with higher CKD stage ( P < .001). The highest in-hospital mortality occurred in patients with coprevalence of CKD stage 4 and Fontaine stage IV (16.4%, n = 1176, P < .001). Chronic kidney disease caused 15% higher costs and 21% increased length of stay compared to the whole PAD cohort. This analysis demonstrates the stage-related influence of CKD on morbidity, in-hospital mortality, amputations, length of hospital stay, and reimbursement costs of hospitalized patients with PAD.

Abstract 16894: The Effect of Cangrelor on Cardiovascular and Bleeding Events in Patients With Peripheral Artery Disease - Insights From CHAMPION PHOENIX

Background: Patients with peripheral artery disease (PAD) are high risk for adverse cardiovascular and bleeding events. In CHAMPION-PHOENIX, cangrelor, an intravenous P2Y12 inhibitor, reduced rates of ischemic events in patients undergoing PCI. Hypothesis: We hypothesize that cangrelor will safely reduce ischemic events in patients with PAD undergoing PCI. Methods: A total of 11,145 patients were randomly assigned in a double-dummy, double-blind manner to either cangrelor followed by clopidogrel 600 mg or to clopidogrel loading at PCI. The primary endpoint was a composite of death, MI, ischemia-driven revascularization (IDR), or stent thrombosis (ST) at 48 hours. Results: 837 (8%) patients with PAD and 9,994 (90%) patients with no prior history of PAD underwent PCI. Among the PAD cohort the primary endpoint occurred in 20 (4.5%) cangrelor vs. 44 (11.4%) clopidogrel patients (OR [95% CI] = 0.36 [0.21, 0.63]), and 235 (4.7%) cangrelor vs. 276 (5.5%) clopidogrel patients (OR [95%CI] = 0.86 [0.72, 1.03]) without PAD (p for interaction = 0.003). Among the PAD cohort the rate of GUSTO severe/life-threatening bleeding was 0.4% cangrelor vs. 0% clopidogrel (p = 0.19), and 0.1% cangrelor vs. 0.1% clopidogrel patients (OR [95%CI] = 1.78 [0.52, 6.07], p = 0.35) without PAD (p for interaction = 0.34). The rate of blood transfusion in the PAD cohort was 0.9% cangrelor vs. 0% clopidogrel (p = 0.06), and 0.4% cangrelor vs. 0.3% clopidogrel patients (OR [95%CI] = 1.42 [0.73, 2.76], p = 0.30) without PAD (p for interaction = 0.13). Conclusion: In CHAMPION-PHOENIX, cangrelor significantly reduced ischemic events with no significant increase in severe bleeding or transfusions in patients with PAD.