Severity Of Peripheral Arterial Disease Research Articles

Abstract 722: Evaluation of Peripheral Calcium Score as a Measure of Peripheral Artery Disease Severity

The current gold standard for diagnosing PAD is Ankle Brachial Index (ABI). However, vascular calcification can falsely elevate ABI. No studies have compared the diagnostic value of peripheral calcium score (PCS) in lower extremity arteries with ABI. Primary aim of this study was to describe the association of PCS with continuous ABI values and categories of ABI in a retrospective cohort design. We identified 50 patients who underwent CTA and ABI measurements [ABI categories for PAD severity: severe (<0.5), moderate (0.5-0.9), normal (0.9-1.4), noncompressible (>1.4)]. We evaluated CTAs imaged from abdominal aorta through lower extremities and determined total calcium volume of plaques with density >130 HU and area >1mm 2 from infrarenal abdominal aorta to the foot using TeraRecon by two independent readers (Intra class correlation 99%). We explored the association between ABI and PCS in SAS using multiple linear regression and analysis of covariance adjusting for age, race, smoking status, hypertension, hyperlipidemia, type II diabetes, and chronic kidney disease. We found that ABI was inversely associated with PCS in linear regression (p<0.01, Figure 1A). Differences in mean PCS were statistically significant across ABI categories [F(3,29)= 5.03, p=0.01, Figure 1B]. Across subgroups, the mean PCS was significantly different for ABIs <0.5 and 0.5-0.9 (p=0.02), <0.5 and >1.4 (p<0.001), 0.5-0.9 and >1.4 (p=0.04), 0.9-1.4 and >1.4 (p=0.05). Proportion of tibial calcium to overall PCS was much lower in ABI<0.5: 0.0003 vs ABI>1.4: 0.357 (p=0.02). Mean PCS may be a valid measure of PAD severity and percentage of tibial calcium may help quantify PAD burden in non-compressible vessels. Our study serves as proof of concept for a comprehensive PCS system to diagnose and evaluate PAD severity, particularly in high-risk subpopulations where non-invasive studies may be unreliable.

OP-63 - Is There a Relationship between Fragmented Qrs and the Severity of Peripheral Artery Disease?

Background: The purpose of the present study was to analyze the relationship between fragmented QRS (fQRS) and the severity of peripheral artery disease (PAD).

Predictors of health-related quality of life in patients with symptomatic peripheral artery disease

ObjectiveThe aim of this study was to identify predictors of baseline measures of health-related quality of life (HRQoL) in symptomatic patients with peripheral artery disease (PAD) from objective markers of severity of PAD, clinical and demographic characteristics, comorbid conditions, cardiovascular risk factors, objectively measured physical activity, and patient-based measures of physical function. MethodsHRQoL measurements of 216 symptomatic men and women with PAD were assessed with the Medical Outcomes Study 36-Item Short Form Health Survey. Patients were further characterized on demographic variables, comorbid conditions, cardiovascular risk factors, ankle-brachial index, peak walking time during a maximal treadmill test, 6-minute walk distance, gait speed, ambulatory activity monitored during 1 week, activities of daily living (ADLs), Mini-Mental State Examination questionnaire, and Walking Impairment Questionnaire (WIQ). ResultsFor the physical function HRQoL subscale, the significant predictors included WIQ speed score (P < .001), history of stumbling (P < .001), WIQ stair climbing score (P < .001), ADL associated with bathing (P = .001), 6-minute walk distance (P = .004), and daily walking cadence (P = .043). For the role emotional function HRQoL subscale, the significant predictors included a history of stumbling (P < .001), the ADL associated with transferring from a bed to a chair (P < .001), and the WIQ distance score (P = .022). ConclusionsPhysical and mental subscales of HRQoL in symptomatic patients with PAD are primarily predicted by patient-based physical function rather than by more specific markers of PAD severity and comorbid conditions. The clinical significance is that interventions designed to improve HRQoL should focus on improving the quality of executing functional tasks, such as walking more steadily without stumbling; completing ADLs that are not specific to walking, such as bathing and transferring; and improving patient-based ability to walk various distances and speeds and to climb stairs.

Abstract P369: Relation of Breast Arterial Calcification With Ankle Brachial Index

Presence of breast arterial calcification (BAC) has been shown to be independently associated with increased risk of subclinical cardiovascular disease (CVD), angiographically-defined coronary disease and with incident coronary heart disease, stroke and heart failure. However, a relationship between BAC and peripheral vascular disease has not been established. The ankle brachial index (ABI) is an indicator of the severity of peripheral arterial disease (PAD) that predicts future CVD risk. We utilized cross-sectional data collected at the baseline examination (2012-15) of the MultIethNic Study of BrEast ARterial Calcium Gradation and CardioVAscular Disease (MINERVA Study), a cohort study of 5,145 post-menopausal women who were members of the Kaiser Permanente Medical Care Program of Northern California (KPNC) who were free of clinical CVD at baseline. Presence and gradation (in mg of calcium mass) of BAC in digital mammograms was ascertained with a validated densitometry method. ABI, the average of two ankle systolic pressure readings divided by the average of two brachial systolic pressure readings, was measured by trained and certified personnel after a ten-minute rest. A total of 3,693 women had complete data on all variables of interest; their mean (SD) age was 66 (4) years and 64% were white, 12% African-American, 14% Asian, 9% Latina and 1% mixed or other. While 28.2% presented with any detectable BAC (i.e., BAC mass &gt; 0 mg), 5.4% had an ABI &lt; 0.90. Three women had ABI&gt;1.40 and were excluded from analyses (none had BAC&gt;0). Prevalence of ABI &lt; 0.90 was 4.8% (27/2,653) in women with BAC=0 and 6.9% (72/1,040) in women with any detectable BAC. The Odds Ratio of ABI&lt;0.90 associated with any BAC was 1.39 (95% CI, 1.03-1.89) in a model adjusting for age and race/ethnicity, and was 1.38 (95% CI, 1.02-1.88) in a model with further adjustment for BMI, smoking status, diabetes, hypertension, LDL cholesterol, HDL cholesterol and hs-CRP. However, among women with any detectable BAC, standardized log_BAC mass (mg) was not significantly associated in bivariate linear regression analysis with ABI (slope=-0.0030 [SE=0.0031]; p=0.32). Our study demonstrates (for the first time) an independent association between presence of BAC and ABI indicative of PAD, with no apparent linear dose-response relationship.

Association of serum C1q tumour necrosis factor–related protein 9 with the severity of lower extremity peripheral arterial disease in type 2 diabetes patients

Recent studies have indicated the implication of C1q tumour necrosis factor-related protein 9 in vascular pathology of atherosclerosis. This study first investigated the association of C1q tumour necrosis factor-related protein 9 and the severity of lower extremity peripheral arterial disease in type 2 diabetes mellitus patients. A total of 200 patients with type 2 diabetes mellitus had ankle-brachial index examined in this cross-sectional study, 60 patients with ankle-brachial index of ⩽0.9 were diagnosed with peripheral arterial disease and further classified into mild, moderate and severe group with Vivid 7 diagnostic apparatus. C1q tumour necrosis factor-related protein 9 and adiponectin were higher in diabetes mellitus with severe peripheral arterial disease than diabetes mellitus with mild and moderate peripheral arterial disease groups. After adjustment of conventional atherosclerosis risk factors, C1q tumour necrosis factor-related protein 9 ( r = -0.627, p < 0.001) and adiponectin ( r = -0.431, p = 0.003) were negatively correlated with the severity of peripheral arterial disease. Logistic regression analysis showed C1q tumour necrosis factor-related protein 9 was independently associated with the severity of peripheral arterial disease (odds ratio = 0.272, 95% confidence interval = 0.08-0.927, p = 0.037). Serum C1q tumour necrosis factor-related protein 9 is negatively and independently associated with the severity of peripheral arterial disease in type 2 diabetes mellitus patients, suggesting the protective potentials of C1q tumour necrosis factor-related protein 9 in the progression of peripheral arterial disease in human type 2 diabetes mellitus.

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

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. 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. 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. 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.

The relationship between medical expenses and the severity of peripheral arterial disease in Japan.

The main objective is to examine whether the severity of peripheral arterial disease (PAD) affects the expenses and hospital stay of the patients who undergo bypass surgery below the inguinal ligament for PAD. Eighty consecutive patients who underwent infrainguinal bypass surgery for PAD between January 2012 and December 2014 were included in the study. Patients were divided into groups according to their critical limb ischemia (CLI) symptoms and the Wound, Ischemia, and Foot Infection (WIfI) classification. As endpoints, we assessed the duration of postoperative hospital stay and expenses during hospitalization. CLI was a significant factor for longer hospital stay and increased medical expenses (p=0.009 and p=0.001). In the patients with CLI, significant factors for longer hospital stay and increased medical expenses were (1) history of distal bypass (p=0.33 and p=0.003, respectively) and stage 4 local lower limb status in WIfI classification (p=0.0007 and p=0.053). PAD severity was associated with prolonged postoperative hospital stay and increased medical expenses. The presence or absence of CLI and its severity according to the WIfI classification correlated with medical expenses and hospital stay duration between the milder and severe groups.

Evaluation of skeletal muscle microvascular perfusion of lower extremities by cardiovascular magnetic resonance arterial spin labeling, blood oxygenation level-dependent, and intravoxel incoherent motion techniques

BackgroundNoninvasive cardiovascular magnetic resonance (CMR) techniques including arterial spin labeling (ASL), blood oxygenation level-dependent (BOLD), and intravoxel incoherent motion (IVIM), are capable of measuring tissue perfusion-related parameters. We sought to evaluate and compare these three CMR techniques in characterizing skeletal muscle perfusion in lower extremities and to investigate their abilities to diagnose and assess the severity of peripheral arterial disease (PAD).MethodsFifteen healthy young subjects, 14 patients with PAD, and 10 age-matched healthy old subjects underwent ASL, BOLD, and IVIM CMR perfusion imaging. Healthy young and healthy old participants were subjected to a cuff-induced ischemia experiment with pressures of 20 mmHg and 40 mmHg above systolic pressure during imaging. Perfusion-related metrics, including blood flow, T2* relaxation time, perfusion fraction f, diffusion coefficient D, and pseudodiffusion coefficient D*, were measured in the anterior, lateral, soleus, and gastrocnemius muscle groups. Friedman, Mann-Whitney, Wilcoxon signed rank, and Spearman rank correlation tests were used for statistical analysis.ResultsIn cases of significant differences determined by the Friedman test (P < 0.05), blood flow, T2*, and D values gradually decreased, while f values showed a tendency to increase in healthy subjects under cuff compression. No significant correlations were found among the ASL, BOLD, and IVIM parameters (all P > 0.05). Blood flow and T2* values showed significant positive correlations with transcutaneous oxygen pressure measurements (ρ = 0.465 and 0.522, respectively; both P ≤ 0.001), while f values showed a significant negative correlation in healthy young subjects (ρ = − 0.351; P = 0.018). T2* was independent of age in every muscle group. T2* values were significantly decreased in PAD patients compared with healthy old subjects and severe PAD patients compared with mild-to-moderate PAD patients (all P < 0.0125). Significant correlations were found between T2* and ankle–brachial index values in all muscle groups in PAD patients (ρ = 0.644–0.837; all P < 0.0125). Other imaging parameters failed to show benefits towards the diagnosis and disease severity evaluation of PAD.ConclusionsASL, BOLD, and IVIM provide complementary information regarding tissue perfusion. Compared with ASL and IVIM, BOLD may be a more reliable technique for assessing PAD in the resting state and could thus be applied together with angiography in clinical studies as a tool to comprehensively assess microvascular and macrovascular properties in PAD patients.

Toe-brachial index and exercise test can improve the exploration of peripheral artery disease

Background and aimsWe assumed that hand-held Doppler ultrasound (DUS) at rest was insufficient to assess the severity of peripheral artery disease (PAD). Toe pressure and transcutaneous tissue oxygen pressure were studied to prove whether these could identify more patients with severe lower limb ischemia; exercise was applied to provoke ischemia. Methods120 patients with PAD and 30 volunteers without PAD were recruited. DUS, transcutaneous tissue oxygen pressure (tcpO2) and toe pressure measurements were performed at rest and after exercise. The differential power of these examinations for severe limb ischemia (SLI) was determined by receiver-operating curves (ROCs) and pattern recognition by independent multicategory analysis (PRIMA). ResultsThere was an obvious significant difference between the patient and control groups at rest; after exercise; the ratio of severely impaired values (ankle-brachial index – ABI, toe-brachial index – TBI, tcpO2 measured on index forefoot) increased significantly in the patient group (p < 0.05). TBI, tcpO2, ABI measured after exercise could differentiate SLI better than the values of these tests at rest (p < 0.001). In ROC analysis, the largest area under the curve (AUC) was covered by post- (AUC: 0.860) and pre-exercise TBI (AUC: 0.785), and post-exercise tcpO2 (AUC: 0.720) (p < 0.001). Post-exercise TBI gained the best discriminant score in PRIMA. ConclusionsPre- and post-exercise non-invasive vascular tests could reveal severe limb ischemia. Toe pressure measurement and TBI should become a basic part of the vascular workup.

Osteoprotegerin concentration is associated with the presence and severity of peripheral arterial disease in type 2 diabetes mellitus.

Osteoprotegerin plays a role in the development of several bone diseases. In addition, osteoprotegerin may contribute to the development of vascular disease. Little is known about the association between serum osteoprotegerin levels and the presence or severity of peripheral arterial disease (PAD). The aim of this study was to examine the association between serum osteoprotegerin levels and both the presence as well as the severity of lower extremity arterial disease in patients with type 2 diabetes (T2DM). The study included 165 consecutive patients with T2DM (57 % males, mean age 65.0 ± 0.7 years). PAD was diagnosed by measurement of the toe-brachial index (TBI). Serum osteoprotegerin was measured using ELISA. The mean osteoprotegerin level was significantly higher in patients with PAD in comparison to patients without PAD (18.2 ± 1.0 vs. 13.1 ± 2.0 pmol/L, p = 0.014). Significant univariate correlations between TBI and osteoprotegerin level (r = -0.308; p < 0.001), age, body mass index, and HDL cholesterol were observed. In the multivariate linear regression analysis, serum osteoprotegerin (β = -0.005; p = 0.020), higher age, and male gender were significant predictors of TBI. When 25(OH) vitamin D was introduced into the mentioned model, OPG was no longer a significant predictor of TBI and was replaced in the model with vitamin D (β = 0.009, p = 0.001). This finding suggests a role of OPG as a mediator of the effects of 25(OH) vitamin D. Serum osteoprotegerin level is significantly associated with both the presence and severity of PAD in patients with T2D. Osteoprotegerin might be a biomarker for the presence of atherosclerotic disease in patients with T2DM.

Role of genetics in peripheral arterial disease outcomes; significance of limb-salvage quantitative locus-1 genes.

Peripheral artery disease is a major health care problem with significant morbidity and mortality. Humans with peripheral artery disease exhibit two major and differential clinical manifestations - intermittent claudication and critical limb ischemia. Individuals with intermittent claudication or critical limb ischemia have overlapping risk factors and objective measures of blood flow. Hence, we hypothesized that variation in genetic make-up may be an important determinant in the severity of peripheral artery disease. Previous studies have identified polymorphism in genes, contributing to extent of atherosclerosis but much less is known about polymorphisms associated with genes that can influence peripheral artery disease severity. This review outlines some of the progress made up-to-date to unravel the molecular mechanisms underlining differential peripheral artery disease severity. By exploring the recovery phenotype of different mouse strains following experimental peripheral artery disease, our group identified the limb salvage-associated quantitative trait locus 1 on mouse chromosome 7 as the first genetic modifier of perfusion recovery and tissue necrosis phenotypes. Furthermore, a number of genes within LSq-1, such as ADAM12, IL-21Rα, and BAG3 were identified as genetic modifiers of peripheral artery disease severity that function through preservation of endothelial and skeletal muscle cells during ischemia. Taken together, these studies suggest manipulation of limb salvage-associated quantitative trait locus 1 genes show great promise as therapeutic targets in the management of peripheral artery disease. Impact statement Peripheral artery disease (PAD) is a major health care problem with significant morbidity and mortality. Individuals with similar atherosclerosis burden do display different severity of disease. This review outlines some of the progress made up-to-date in unraveling the molecular mechanisms underlining differential PAD severity with a focus on the role of the Limb Salvage-associated Quantitative trait locus 1 (LSq-1), a key locus in adaptation to ischemia in PAD.

Nationwide Trends in Hospital Outcomes and Utilization After Lower Limb Revascularization in Patients on Hemodialysis

ObjectivesThis study aimed to describe the temporal trends and outcomes of endovascular and surgical revascularization in a large, nationally representative sample of patients with end-stage renal disease on hemodialysis hospitalized for peripheral artery disease (PAD). BackgroundPAD is prevalent among patients with end-stage renal disease on hemodialysis and is associated with significant morbidity and mortality. There is a paucity of information on trends in endovascular and surgical revascularization and post-procedure outcomes in this population. MethodsWe used the Nationwide Inpatient Sample (2002 to 2012) to identify hemodialysis patients undergoing endovascular or surgical procedures for PAD using diagnostic and procedural codes. We compared trends in amputation, post-procedure complications, mortality, length of stay, and costs between the 2 groups using trend tests and logistic regression. ResultsThere were 77,049 endovascular and 29,556 surgical procedures for PAD in hemodialysis patients. Trend analysis showed that endovascular procedures increased by nearly 3-fold, whereas there was a reciprocal decrease in surgical revascularization. Post-procedure complication rates were relatively stable in persons undergoing endovascular procedures but nearly doubled in those undergoing surgery. Surgery was associated with 1.8 times adjusted odds (95% confidence interval: 1.60 to 2.02) for complications and 1.6 times the adjusted odds for amputations (95% confidence interval: 1.40 to 1.75) but had similar mortality (adjusted odds ratio: 1.05; 95% confidence interval: 0.85 to 1.29) compared with endovascular procedures. Length of stay for endovascular procedures remained stable, whereas a decrease was seen for surgical procedures. Overall costs increased marginally for both procedures. ConclusionsRates of endovascular procedures have increased, whereas those of surgeries have decreased. Surgical revascularization is associated with higher odds of overall complications. Further prospective studies and clinical trials are required to analyze the relationship between the severity of PAD and the revascularization strategy chosen.

Prevalence and severity of peripheral arterial disease among patient with heel pressure ulcer: a retrospective study of 42 patients.

Heel pressure ulcer is a major complication in elderly hospitalized patients. The association with peripheral arterial disease (PAD) which is also a frequent disease in this population is poorly known. The aim of this study was to assess the prevalence of PAD and critical limb ischemia (CLI) in patients with heel pressure ulcer. Patients referred to the vascular medicine department for heel pressure ulcer from October 2014 to June 2015 were included in the study. The assessment of peripheral arterial disease was made with the results of ankle brachial index and/or doppler ultra sound of lower limb arteries. Toe systolic pressure and transcutaneous pressure (TcPO2) were also recorded, and the diagnosis of critical limb ischemia was made according to the TASC 2 criteria. The population was composed with 42 patients (women 43%, men 57%). The mean age was 81±11 years. Heel pressures ulcers were diagnosed in the following situations: lower limb fracture (31%), acute medical illness (21%), multiple chronic conditions (28%) and critical care unit hospitalization (7%). A peripheral arterial disease was present in 31 patients (73%), and a critical limb ischemia in 7 patients. For 18 patients, PAD was not known in their past medical history, and this was the case of 5 patients among those with critical limb ischemia. A revascularization was performed in 12 patients, and 5 patients undergo a lower limb amputation. 12 patients were died at 3 months. PAD is frequent among patients with heel pressure ulcer, and is often unknown. The functional and vital prognostic are poor, and the results of our study emphasize the importance of screening PAD in the evaluation of heel pressure ulcer risk.

High hemoglobin A1c associated with increased adverse limb events in peripheral arterial disease patients undergoing revascularization

ObjectiveDiabetes and peripheral arterial disease (PAD) are independently associated with increased risk of amputation. However, the effect of poor glycemic control on adverse limb events has not been studied. We examined the effects of poor glycemic control (high hemoglobin A1c level) on the risk of amputation and modified major adverse limb events (mMALEs) after lower extremity revascularization. MethodsPatients undergoing PAD revascularization who had hemoglobin A1c (HbA1c) levels available within 6 months were identified in the Veterans Affairs database of 2003 to 2014 (N = 26,799). The diagnosis of preoperative diabetes mellitus (PreopDM) was defined using diabetes diagnosis codes and evidence of treatment. Amputation and mMALE risk was compared for HbA1c levels using Kaplan-Meier analysis. Cox proportional hazards models were created to assess the effect of high HbA1c levels on amputation and mMALE (adjusted for age, gender, race, socioeconomic status, comorbidities, cholesterol levels, creatinine concentration, suprainguinal or infrainguinal procedure, open or endovascular procedure, severity of PAD, year of cohort entry, and medications) for all patients and stratified by PreopDM. ResultsHigh HbA1c levels were present in 33.2% of the cohort, whereas 59.9% had PreopDM. Amputations occurred in 4359 (16.3%) patients, and 10,580 (39.5%) had mMALE. Kaplan-Meier curves showed the worst outcomes in patient with PreopDM and high HbA1c levels. In the Cox model, incremental HbA1c levels of 6.1% to 7.0%, 7.1% to 8.0%, and >8% were associated with 26% (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.15-1.39), 53% (HR, 1.53; 95% CI, 1.37-1.7), and 105% (HR, 2.05; 95% CI, 1.87-2.26) higher risk of amputation, respectively. Similarly, the risk of mMALE also increased by 5% (HR, 1.05; 95% CI, 0.99-1.11), 21% (HR, 1.21; 95% CI, 1.13-1.29), and 33% (HR, 1.33, 95% CI, 1.25-1.42) with worsening HbA1c levels of 6.1% to 7.0%, 7.1% to 8.0%, and >8%, respectively (vs HbA1c ≤6.0%). In stratified analysis by established PreopDM, the relative risk of amputation or mMALE was much higher with poor glycemic control (HbA1c >7.0%) in patients without PreopDM. ConclusionsPAD patients with worse perioperative glycemic control have a significantly higher risk of amputation and mMALE. Incremental increases in HbA1c levels are associated with higher hazards of adverse limb outcomes independent of PreopDM status. Poor glycemic control (HbA1c >7.0%) in patients without a PreopDM diagnosis carries twice the relative risk of amputation and mMALE than in those with good glycemic control. These results suggest that screening of diabetic status and better management of glycemic control could be a target for improvement of perioperative and long-term outcomes in PAD patients.

Serum high mobility group box-1 and osteoprotegerin levels are associated with peripheral arterial disease and critical limb ischemia in type 2 diabetic subjects

BackgroundHigh mobility group box-1 (HMGB-1) is a nuclear protein also acting as inflammatory mediator, whilst osteoprotegerin (OPG), member of tumor necrosis factor receptor superfamily, is indicated as marker of vascular calcification. Peripheral artery disease (PAD) and type 2 diabetes (T2D) are clinical conditions characterized by elevated serum inflammatory markers and vascular calcification enhancement. The aim of this study was to investigate the potential role of HMGB-1, OPG and several inflammatory mediators such as C-reactive protein (HsCRP), tumor necrosis factor-alpha and interleukin-6 (IL-6) on the presence and severity of peripheral artery disease in patients with T2D.MethodsIn this retrospective observational study, we have analyzed HMGB-1, OPG and inflammatory cytokines serum levels in 1393 type 2 diabetic patients with PAD and without PAD (WPAD).ResultsHMGB-1 (7.89 ± 15.23 ng/mL), OPG (6.54 ± 7.76 pmol/L), HsCRP (15.6 ± 14.4 mg/L) and IL-6 (56.1 ± 28.6 pg/mL) serum levels were significantly higher in patients with PAD than in those WPAD (3.02 ± 8.12 ng/mL, P ˂ 0.001; 2.98 ± 2.01 pmol/L, P < 0.001; 7.05 ± 4.4 mg/L, P < 0.001; 37.5 ± 20.2 pg/mL, P < 0.001 respectively). Moreover HMGB-1 (P < 0.001), OPG (P < 0.001), HsCRP (P < 0.001) and IL-6 (P < 0.001) serum levels were positively correlated with clinical severity of PAD. HMGB-1 (adjusted OR 12.32; 95% CI 3.56–23.54, P = 0.023) and OPG (adjusted OR 3.53; 95% CI 1.54–6.15, P = 0.019) resulted independent determinants of PAD in patients with T2D after adjusting for the conventional cardiovascular risk factor and established inflammatory mediators.ConclusionsIn T2D patients HMGB-1 and OPG serum levels are higher in patients affected by PAD and independently associated with its occurrence and clinical severity.

Sleep apnoea is common in severe peripheral arterial disease.

BackgroundAtherosclerotic conditions have been demonstrated to be associated with sleep- disordered breathing (SDB). Peripheral arterial disease (PAD) represents severe atherosclerosis with a high mortality. In early stages of PAD a substantial prevalence of sleep apnoea has already been shown. Here, we sought to determine the frequency of undiagnosed sleep apnoea in a homogeneous group of advanced PAD patients undergoing percutaneous revascularization.Methods59 consecutive patients (mean age: 71.1 ± 9.8 years, 67.8% males) with PAD in Fontaine stages IIb-IV that underwent percutaneous transluminal angioplasty at our department were enrolled for pre-procedural polygraphy.ResultsPatients appertained to Fontaine clinical stage IIb, III and IV in 54.2%, 23.8% and 22.% of cases, respectively, and were principally intervened for femoropopliteal occlusive disease (71.2% of total study population). Polygraphy revealed sleep apnoea in 48 out of 59 patients (81.4%), of whom 60.4% offered a primarily obstructive-driven genesis. Among those patients with polygraphically confirmed sleep apnoea, mean apnoea hypopnoea index (AHI) and mean oxygen desaturation index (ODI) averaged 28.2 ± 19.5/h and 26.7 ± 18.8/h, respectively. 18 patients even offered an AHI ≥30/h that is indicative of severe sleep apnoea. For obstructive-driven apnoeic events, AHI correlated significantly with PAD severity stages (p = 0.042).ConclusionsIn our PAD collective, sleep apnoea was frequent and obstructive sleep apnoea´s severity correlated with PAD severity stages. Long-term results regarding the vasoprotective impact of CPAP treatment on PAD course remains to be determined.

A Toe Flexion NIRS assisted Test for Rapid Assessment of Foot Perfusion in Peripheral Arterial Disease: Feasibility, Validity, and Diagnostic Accuracy

Feasibility, validity, and diagnostic accuracy of a non-invasive dynamic ambulatory test were assessed with near infrared spectroscopy (NIRS) evaluating foot perfusion in peripheral arterial disease (PAD). This was a prospective observational study. Eighty PAD patients (63 males, 71±9 years), including 41 patients with coexisting diabetes, participated. Thirteen healthy subjects (8 males, 26±8 years) were also studied by echo colour Doppler providing 160 diseased and 26 non-diseased limbs. Under identical clinostatic conditions, participants performed a 10-repetition toe flexion tests with NIRS probes on the dorsum of each foot; the area under the curve of the oxygenated haemoglobin trace ("toflex area") was calculated and the ankle-brachial index (ABI) was measured. Time of execution, rate of wrong tests, and adverse reactions were recorded. Within session reliability was assessed by administering the test twice, with a 5 minute interval between tests. The validity was assessed determining whether the toflex area was (a) dependent on the oxygen delivery from the lower limb arteries simulating PAD conditions by a progressive blood flow restriction (40-120% of systolic pressure) in healthy subjects; (b) consistent with the degree of PAD ranked by ABI and correlated with ABI and ankle pressure values in PAD patients. The diagnostic accuracy in detecting PAD was compared with examination using echo colour Doppler ultrasound. All tests were rapidly, satisfactorily (<1% mistakes), and safely performed. Toflex area values, superimposable in the two sessions (intra-class correlation coefficient 0.92), were comparable to PAD values following blood flow restriction, consistent with PAD severity, correlated with dorsal pedis artery pressure (r=.21; p=.007) and ABI (r=.65; p<.001) in PAD, but not in the presence of diabetes. Toflex area was similar to echo colour Doppler for detecting PAD following receiver operating characteristic curve analysis (area=0.987, p<.001; toflex area values≤-28arbitrary units, sensitivity/specificity 95.6/100). The toe flexion test enables ambulatory assessment of foot perfusion and PAD detection, even in the presence of non-measurable ABI or diseases affecting the microcirculation.

Toe Pressure and Toe Brachial Index are Predictive of Cardiovascular Mortality, Overall Mortality, and Amputation Free Survival in Patients with Peripheral Artery Disease

Peripheral haemodynamic parameters are used to assess the presence and severity of peripheral artery disease (PAD). The prognostic value of ankle brachial index (ABI) has been thoroughly delineated. Nonetheless, the relative usefulness of ankle pressure (AP), ABI, toe pressure (TP), and toe brachial index (TBI) in assessing patient outcome has not been investigated in a concurrent study setting. This study aimed to resolve the association of all four non-invasive haemodynamic parameters in clinically symptomatic patients with PAD with cardiovascular mortality, overall mortality, and amputation free survival (AFS). In total, 732 symptomatic patients with PAD admitted to the Department of Vascular Surgery for conventional angiography at Turku University Hospital, Turku, Finland, between January 2009 and August 2011 were reviewed retrospectively. Demographic factors, cardiovascular mortality, all-cause mortality, and above foot level amputations were obtained and assessed in relation to AP, ABI, TP, and TBI by means of Kaplan-Meier life tables and a multivariate Cox regression model. The haemodynamic parameter that was associated with poor 36 month general outcome was TP < 30mmHg. Univariate Cox regression analysis of stratified values showed that TP and TBI associated significantly with mortality. In multivariate analysis both TP and TBI were associated with a significant risk of death. For TP < 30mmHg and TBI < 0.25 the risk of cardiovascular mortality was hazard ratio [HR] 2.84, 95% confidence interval [CI] 1.75-4.61 [p<.001]; HR 3.68, 95% CI 1.48-9.19 [p=.050], respectively; all-cause mortality (HR 2.05, 95% CI 1.44-2.92 [p<.001]; HR 2.53, 95% CI 1.35-4.74 [p=.040], respectively); and amputation or death (HR 2.13, 95% CI 1.52-2.98 [p<.001]; HR 2.46, 95% CI 1.38-4.40 [p=.050], respectively)... Among non-invasive haemodynamic measurements and pressure indices both TP and TBI appear to be associated with cardiovascular and overall mortality and AFS for patients with PAD presenting symptoms of the disease.

Abstract 111: Health Status Implications for Comorbid Diabetes in Patients with Symptomatic Peripheral Arterial Disease: Insights from PORTRAIT Registry

Introduction: Patients with peripheral arterial disease (PAD) and coexisting diabetes mellitus (DM) have an increased rate of PAD progression and reduced walking performance as compared with non-diabetic PAD patients. It is unknown, however, whether patients with PAD and comorbid diabetes also experience worse PAD-specific health status (symptoms, functioning, quality of life) and what factors might mediate such a difference. Methods: PORTRAIT is a 16-center international registry that includes patients with exacerbated or new-onset symptomatic PAD presenting to specialty clinics. We measured PAD-specific health status at the time of PAD evaluation, 3, 6 and 12 months using the Peripheral Artery Questionnaire (PAQ). Hierarchical, multivariable, repeated measures analysis was used to assess the association between DM and health status at baseline and over time. Sequential adjustments for demographics, socioeconomic factors, PAD severity, comorbidities, psychosocial characteristics, primary treatment strategy and quality of care were made. Results: Of 1,204 patients, 398 patients had diabetes (33%, of whom 94% had Type II). Patients with PAD and DM had lower unadjusted PAQ summary scores at 0, 3, 6 and 12 months respectively (46.1 vs. 50.8, p &lt; 0.001; 63.6 vs. 68.2, p &lt; 0.01; 65.7 vs. 71.7, p &lt; 0.001; 65.4 vs. 72.6, p &lt;0.001). Patients with PAD and DM were more likely to be unemployed, depressed, of non-White race and to have more cardiovascular comorbidities, bilateral disease, non-healing ulcers and prior peripheral vascular interventions. When sequentially adjusting for relevant confounders, the effect for diabetes was mostly explained by comorbidities and psychosocial factors (Figure 1). Conclusion: Patients with PAD and co-existing DM have poorer health status upon PAD diagnosis and the year thereafter as compared with those who do not have DM, potentially explained by a higher burden of clinical comorbidities and psychosocial factors. Future work will need to further evaluate whether more emphasis on psychosocial aspects of care in these patients can improve their PAD-specific health status.

Abstract 056: Age-specific Differences in Baseline Characteristics, Peripheral Arterial Disease Specific Health Status, and Patterns of Care in Patients With Peripheral Arterial Disease: Insights From the Patient-centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories (PORTRAIT) Registry

Background: The aging population along with the increased use of statins, anti-platelet agents, supervised exercise (SE) and smoking cessation (SC) may be altering the epidemiology of peripheral arterial disease (PAD) and may be delaying its onset. There are no insights into how older versus younger patients differ in terms of PAD severity, risk profiles, health status and treatment. We hypothesized that in the absence of any reliable age-related differences in treatment effectiveness, that risk reduction and revascularization would be used equally across PAD age cohorts. Aim: Assess age-specific differences in baseline characteristics, PAD-specific health status, and patterns of care in patients in the PORTRAIT registry. Methods: The PORTRAIT registry prospectively collected data from 1275 patients with new or worsening PAD symptoms who were treated in the US, the Netherlands or Australia between June 2011 and October 2015. Patients were grouped by age (&lt; 60 years, 60 to ≤75 years, and &gt; 75 years). We compared patient characteristics at the point of seeking specialty PAD care, including severity of PAD (Rutherford classification); health status assessed by the Peripheral Artery (PAQ) and EuroQol five dimensions (EQ5D) questionnaires; and subsequent clinical care offered for PAD, including statins, anti-platelet agents, SE, and SC. The use of revascularization (surgical or endovascular) was assessed at 3 months. Continuous variables were compared using the linear trend test. Categorical variables were compared using Mantel-Haenszel trend test. Results: There were 303 patients &lt; 60 years (mean 55.0 ± 4.3), 675 patients 60 to ≤75 years (mean 67.8 ± 3.9), and 297 patients ≥ 75 years (mean 79.9 ± 4.1). There were no differences in baseline ABI (mean 0.66 ± 0.2, p=0.44) or Rutherford classification (p=0.47). PAQ summary, quality of life, social limitation, and symptom scores as well as EQ5D scores were significantly worse in patients &lt; 60 years (p&lt;0.001 for all indicators). Patients &lt; 60 years were more likely to be current smokers (60.9% vs. 35.4%, vs. 17.5%, p&lt;0.001). Risk reduction and quality of life (QOL) improvement PAD treatments that were comparable across age cohorts included: statins (p=0.10), SC (0.17), and referral for invasive therapy (p=0.34). In contrast, SE was prescribed more in patients &lt; 60 years (p&lt; 0.001) while anti-platelet therapy was used less often in this group (p=0.025). Conclusion: These data demonstrate that younger patients are characterized by worse PAD-specific health status at the time of entry into vascular specialty care and that there are age-related disparities in the prescription of PAD risk reduction and QOL improvement therapies. These data cannot document the reasons for these differences. Future quality improvement initiatives might focus on these disparities in presentation and care to improve outcomes in PAD.