Peripheral Arterial Disease Patients Research Articles

UFM1 inhibits hypoxia-induced angiogenesis via promoting proteasome degradation of HIF-1α.

Angiogenesis is crucial for blood flow recovery and ischemic tissue repair of peripheral artery disease (PAD). Exploration of new mechanisms underlying angiogenesis will shed light on the treatment of PAD. Ubiquitin-fold modifier 1 (UFM1), a newly identified ubiquitin-like molecule, has been discovered to be involved in various pathophysiological processes. However, the role of UFM1 in the pathogenesis of PAD, especially in endothelial angiogenesis remains obscure, and we aimed to clarify this issue in this study. We initially found UFM1 was significantly upregulated in gastrocnemius muscles of PAD patients and hind limb ischemia mice. And UFM1 was mainly colocalized with endothelial cells in ischemic muscle tissues. Further, elevated expression of UFM1 was observed in hypoxic endothelial cells. Subsequent genetic inhibition of UFM1 dramatically enhanced migration, invasion, adhesion, and tube formation of endothelial cells under hypoxia. Mechanistically, UFM1 reduced the stability of hypoxia-inducible factor-1α (HIF-1α) and promoted the von Hippel-Lindau-mediated K48-linked ubiquitin-proteasome degradation of HIF-1α, which in turn decreased angiogenic factor VEGFA expression and suppressed VEGFA related signaling pathway. Consistently, overexpression of UFM1 inhibited the angiogenesis of endothelial cells under hypoxic conditions, whereas overexpression of HIF-1α reversed this effect. Collectively, our data reveal that UFM1 inhibits the angiogenesis of endothelial cells under hypoxia through promoting ubiquitin-proteasome degradation of HIF-1α, suggesting UFM1 might serve as a potential therapeutic target for PAD.

Superoxide Dismutase and Clopidogrel: A Potential Role in Peripheral Arterial Disease Treatment.

Oxidative stress plays a crucial role in the pathogenesis of peripheral artery disease (PAD). This study aimed to investigate the effect of clopidogrel on oxidative stress in PAD patients. Seventy subjects were divided into three groups: PAD patients before treatment (B-PAD), PAD patients after treatment with clopidogrel (A-PAD), and healthy controls. Serum levels of superoxide dismutase (SOD), copper (Cu), zinc (Zn), manganese (Mn), and oxidized protein were measured. SOD activities were also determined. The results showed that SOD activities, and SOD specific activities were significantly decreased in PAD patients compared to healthy individuals. After treatment with clopidogrel, SOD activities, and SOD specific activities were continuously decrease in PAD patients. The SOD and oxidized protein concentrations were significantly increased in PAD patients compared to healthy individuals. After treatment with clopidogrel, the oxidized protein concentration was significantly decreased, while SOD concentration was significantly increased in PAD patients. These findings suggest that the treatment by clopidogrel stimulated the production of the enzyme but the ratio of active enzyme remained low. The decrease in oxidized protein can be explained by the treatment having antioxidant efficacy that may have compensated for the deficiency in enzyme activity and led to a decrease in oxidized protein. Additionally, the results of this study provide promising evidence that oxidative stress biomarkers including SOD concentration, T-SOD activity, Mn-SOD activity, and oxidized protein levels have potential utility in the diagnosis and management of PAD.

Effects of Acute Hyperoxia on Autonomic Function and Coronary Tone in Patients with Peripheral Artery Disease.

Numerous studies have shown that oxidative stress plays an important role in peripheral artery disease (PAD). Prior reports suggested autonomic dysfunction in PAD. We hypothesized that responses of the autonomic nervous system and coronary tone would be impaired in patients with PAD during exposure to acute hyperoxia, an oxidative stressor. In 20 PAD patients and 16 healthy, sex and age-matched controls, beat-by-beat heart rate (HR, from ECG) and blood pressure (BP, with Finometer) were recorded for 10 minutes during room air breathing and 5 minutes of hyperoxia. Cardiovagal baroreflex sensitivity and HR variability (HRV) were evaluated as measures of autonomic function. Transthoracic coronary echocardiography was used to assess peak coronary blood flow velocity (CBV) in the left anterior descending coronary artery. Cardiaovagal baroreflex sensitivity at rest was lower in PAD than in healthy controls. Hyperoxia raised BP solely in the patients with PAD, with no change observed in healthy controls. Hyperoxia induced an increase in cardiac parasympathetic activity assessed by the high-frequency component of HRV in healthy controls but not in PAD. Indices of parasympathetic activity were lower in PAD than in healthy controls throughout the trial as well as during hyperoxia. Hyperoxia induced coronary vasoconstriction in both groups, while the coronary perfusion time fraction was lower in PAD than in healthy controls. These results suggest that the response in parasympathetic activity to hyperoxia (i.e., oxidative stress) is blunted and the coronary perfusion time is shorter in PAD patients.

Medical Therapy for Peripheral Artery Disease.

Patients with lower extremity peripheral artery disease (PAD) are at high risk for major adverse cardiovascular events (MACE) and major adverse limb events (MALE). This manuscript will review the current evidence for medical therapy in patients with PAD according to different clinical features and the overall cardiovascular (CV) risk. The management of PAD encompasses non-pharmacologic strategies, including lifestyle modification such as smoking cessation, supervised exercise, Mediterranean diet and weight loss as well as pharmacologic interventions, particularly for high risk patients. Benefits for reduction of CV and limb outcomes have been demonstrated for new therapies, including antithrombotic therapy (i.e., low-dose rivaroxaban plus aspirin), lipid lowering therapy (i.e., proprotein convertase subtilisin/kexin type 9inhibitors), and glucose lowering therapy (i.e., sodium-glucose cotransporter-2inhibitors and glucagon-like peptide-1receptor agonists). However, the adoption of these therapies in PAD remains suboptimal in practice. Implementation science studies have recently shown promising results in PAD patients. Comprehensive medical and non-medical management of PAD patients is crucial to improving patient outcomes, mitigating symptoms, and reducing the risk of MACE and MALE. A personalized approach, considering the patient's overall risk profile and preference, is essential for optimizing medical management of PAD.

Impact of Early Intervention on Health Status Outcomes in Peripheral Artery Disease Patients with Chronic Total Occlusion Lesions Using the PORTRAIT Registry

To analyze the impact of non-invasive and early invasive treatments on health status in patients with lower extremity peripheral arterial disease (PAD) without and with chronic total occlusions (CTO) after 12 months of follow-up. Using the international (U.S., Netherlands, and Australia) observational longitudinal PORTRAIT registry, we included patients with recent PAD symptoms between June 2011 and December 2015. We assessed the PAD-specific health status at initial visit, 3-, 6- and 12-month follow-up using the Peripheral Arterial Questionnaire (PAQ). On a propensity matched-weighted cohort, we compared patients' characteristics by CTO status and treatment groups as early invasive (revascularization in the 3 months) vs. non-invasive (exercise, medical therapies, or smoking cessation). We then assessed the health status trajectory over 12 months, as 3-way interaction between CTO status, and treatment groups, and months, using a multilevel generalized linear regression model for repeated measures adjusted for baseline health status with random effects at sites- and patients-level. We included 581 participants, with mean age of 66.62±9.33 years, 34.3% female, and 90.8% White, of whom 353 (60.8%) without and 228 (39.2%) with a CTO lesion. Respectively, 96 (27.2%) and 70 (30.7%) patients underwent early invasive treatment (d=0.07). While patients with CTO were more likely to have lower resting ABI, multilevel disease, and to experience severe claudication vs. their counterparts (|d|≥0.20); the patients' health status at baseline with CTO was not different from those without CTO, with mean Summary scores of 45.14±20.26 vs. 45.90±21.24 (d=0.04), respectively. The trajectory did not differ by CTO status (interaction CTO status*month: p=0.517) and was higher in early invasive vs. non-invasive treatment (treatment*month: p<0.001), regardless of CTO status (CTO status*treatment: p=0.981 and CTO status*treatment*month: p=0.264). The score increased over time with the largest improvement occurring at 3 months in both non-invasive (non-CTO: +7.82 95%CI 4.03;11.60 and CTO: +9.27 95%CI 4.45;14.09) and early invasive (non-CTO: +26.17 95%CI 20.06; 32.28 and CTO: +24.52 95%CI 17.40;31.64) groups. The mean score in CTO vs. non-CTO did not differ at each timepoint, with the 12-month mean score of 70.26 (95%CI 67.87; 74.65) vs. 71.17 (95% CI 65.91; 76.44) (p=0.99) in the non-invasive treatment and 84.93 (95%CI 78.90;90.97) vs. 79.20 (95%CI 72.77;86.14) (p=0.31) in the early invasive treatment. Patients with symptomatic PAD undergoing early revascularization exhibited higher health status over time vs. those undergoing non-invasive treatment strategy, irrespective of the presence of CTOs. The degree of the improvement was greater in the 3 months following the initial visit, especially in patients undergoing early revascularization.

F-8 | “Racial Disparities in Angioplasty Utilization Without or Without Stenting and Outcomes among Peripheral Arterial Disease Patients: Insights from National Inpatient Sample”

F-8 | “Racial Disparities in Angioplasty Utilization Without or Without Stenting and Outcomes among Peripheral Arterial Disease Patients: Insights from National Inpatient Sample”

Real World Application of WIfI Scores in Peripheral Arterial Disease Patients

The Society for Vascular Surgery wound, ischemia, and foot infection (WIfI) classification system aims to risk stratify patients with chronic limb threatening ischemia (CLTI), predicting both amputation rates and the need for revascularization. However, real-world utilization of the system and whether it accurately predicts outcomes following open revascularization and peripheral interventions is unclear. Therefore, we sought to determine the adoption of the WIfI classification system within a contemporary statewide collaborative as well as the impact of patient factor, and WIfI risk assessment on short- and long-term outcomes. Using data from a large statewide collaborative, we identified patients with CLTI undergoing open surgical revascularization or peripheral vascular intervention (PVI) between 2016 - 2022. The primary exposure was preoperative clinical WIfI stage. Patients were categorized according to the SVS Lower Extremity Threatened Limb Classification System into clinical WIfI stages1, 2, 3, or 4. The primary outcomes were 30-day and 1-year amputation and mortality. Multivariable logistic regression was performed to estimate the association of WIfI stage on post-revascularization outcomes. In the cohort of 17,417 patients, 83.4% (n=14,529) had WIfI stage documented. Peripheral vascular interventions (PVIs) were performed on 57.6% of patients, and 42.4% underwent an open surgical revascularization (OSR). 49.5% of patients were classified as stage 1, 19.3% stage 2, 12.8% stage 3 and 18.3% of patients met stage 4 criteria. Stage 3 and 4 patients had higher rates of diabetes, congestive heart failure, and renal failure, and were less likely to be current or former smokers. One-half of stage 3 patients underwent OSR, while stage 1 patients were most likely to have received a PVI (64%). As WIfI stage increased from 1 to 4, 1-year mortality increased from 12% to 21% (p<0.001), 30-day amputation rates increased from 5% to 38% (p<0.001), and 1-year amputation rates increased from 15% to 55% (p<0.001). Finally, patients who did not have WIfI scores classified had significantly higher 30-day and 1-year mortality, as well as higher 30-day and 1-year amputation rates. The Society for Vascular Surgery WIfI clinical stage is significantly associated with 1-year amputation rates in patients with CLTI following lower extremity revascularization. As nearly 55% of stage 4 patients require a major amputation within one year of intervention, this study supports use of the WIfI classification system in clinical decision making for patients with CLTI.

Integrative Bioinformatics-Gene Network Approach Reveals Linkage between Estrogenic Endocrine Disruptors and Vascular Remodeling in Peripheral Arterial Disease.

Vascular diseases, including peripheral arterial disease (PAD), pulmonary arterial hypertension, and atherosclerosis, significantly impact global health due to their intricate relationship with vascular remodeling. This process, characterized by structural alterations in resistance vessels, is a hallmark of heightened vascular resistance seen in these disorders. The influence of environmental estrogenic endocrine disruptors (EEDs) on the vasculature suggests a potential exacerbation of these alterations. Our study employs an integrative approach, combining data mining with bioinformatics, to unravel the interactions between EEDs and vascular remodeling genes in the context of PAD. We explore the molecular dynamics by which EED exposure may alter vascular function in PAD patients. The investigation highlights the profound effect of EEDs on pivotal genes such as ID3, LY6E, FOS, PTP4A1, NAMPT, GADD45A, PDGF-BB, and NFKB, all of which play significant roles in PAD pathophysiology. The insights gained from our study enhance the understanding of genomic alterations induced by EEDs in vascular remodeling processes. Such knowledge is invaluable for developing strategies to prevent and manage vascular diseases, potentially mitigating the impact of harmful environmental pollutants like EEDs on conditions such as PAD.

Influenza vaccination coverage and determinants of vaccination in peripheral arterial disease patients.

Background: In the latest American Heart Association guidelines, influenza vaccination is recommended for patients with peripheral arterial disease (PAD). The vaccination coverage in this specific population is currently unknown. This study aims to determine the adherence to influenza vaccination in a PAD population and identify associated determinants. Patients and methods. Hospitalized patients and outpatients with PAD from two university departments of vascular medicine were prospectively included. A questionnaire was administered to collect sociodemographic data, cardiovascular risk factors, influenza vaccination status, history of cardiovascular disease, and perception and knowledge about vaccination. Logistic regression was conducted to assess vaccination determinants. Results: Over a six-month period, 494 patients were included (median age 69.5, IQR [63-77], 78% male). Overall, 60.1% were either vaccinated or intended to be (Group 1). Vaccination was associated with age (odds-ratio [OR]=1.055, 95% confidence intervals [95%CI]: 1.035-1.075, p<0.0001), abdominal aorta aneurysm (OR=0.390, 95%CI: 0.229-0.664, p=0.001), chronic obstructive pulmonary disease (OR=0.545, 95%CI: 0.367-0.810, p=0.003), chronic renal disease (OR=0.630, 95%CI: 0.400-0.993, p=0.046), and valvulopathy (OR=2.444, 95%CI: 1.122-5.326, p=0.025). Only 25.3% received vaccination information mainly from their general practitioners. Among patients against vaccination, 59.9% considered themselves not concerned about potential influenza consequences on their PAD, and 37.6% did not intend to change their decision. Conclusions: This study highlights the low adherence to influenza vaccination in the PAD population of 2 university hospital centers. Vaccination is often related to age, and there is a need for adapted information regarding influenza consequences on cardiovascular disease overall, particularly on PAD. Addressing common information and advice about vaccination will be a challenge.

Inflammatory Cells in Adipose Tissue and Skeletal Muscle of Patients with Peripheral Arterial Disease or Chronic Venous Disease: A Prospective, Observational, and Histological Study.

The main goal of this study was to assess whether the presence of peripheral arterial disease (PAD) correlates with increased inflammatory cell infiltration. An observational, single-centre, and prospective study was conducted from January 2018 to July 2022. Clinical characteristics and anthropometric measures were registered. Consecutive PAD patients with surgical indications for a common femoral artery approach and patients with varicose veins with an indication for surgical ligation of the saphenofemoral junction were included. In both groups, samples of sartorius skeletal muscle, subcutaneous adipose tissue (SAT), and perivascular adipose tissue (PVAT) were collected from the femoral region. We analysed the characteristics of adipocytes and the presence of haemorrhage and inflammatory cells in the samples of PVAT and SAT via haematoxylin-eosin staining. We found that patients with PAD had significantly more inflammatory cells in PVAT [16 (43.24%) vs. 0 (0%) p = 0.008]. Analysing SAT histology, we observed that patients with PAD had significantly more CD45+ leucocytes upon immunohistochemical staining [32 (72.73%) vs. 3 (27.27%) p = 0.005]. Upon analysing skeletal muscle histology with haematoxylin-eosin staining, we evaluated skeletal fibre preservation, as well as the presence of trauma, haemorrhage, and inflammatory cells. We registered a significantly higher number of inflammatory cells in patients with PAD [well-preserved skeletal fibres: PAD = 26 (63.41%) vs. varicose veins = 3 (37.50%) p = 0.173; trauma: PAD = 4 (9.76%) vs. varicose veins = 2 (25.00%) p = 0.229; haemorrhage: PAD = 6 (14.63%) vs. varicose veins = 0 (0%) p = 0.248; inflammatory cells: PAD = 18 (43.90%) vs. varicose veins = 0 (0%) p = 0.018]. Patients with PAD had a higher number of inflammatory cells in skeletal muscle and adipose tissue (PVAT and SAT) when compared with those with varicose veins, emphasizing the role of inflammation in this group of patients.

Transcriptomics analysis of long non-coding RNAs in smooth muscle cells from patients with peripheral artery disease and diabetes mellitus

Diabetes mellitus (DM) is a significant risk factor for peripheral arterial disease (PAD), and PAD is an independent predictor of cardiovascular disorders (CVDs). Growing evidence suggests that long non-coding RNAs (lncRNAs) significantly contribute to disease development and underlying complications, particularly affecting smooth muscle cells (SMCs). So far, no study has focused on transcriptome analysis of lncRNAs in PAD patients with and without DM. Tissue samples were obtained from our Vascular Biobank. Due to the sample’s heterogeneity, expression analysis of lncRNAs in whole tissue detected only ACTA2-AS1 with a 4.9-fold increase in PAD patients with DM. In contrast, transcriptomics of SMCs revealed 28 lncRNAs significantly differentially expressed between PAD with and without DM (FDR < 0.1). Sixteen lncRNAs were of unknown function, six were described in cancer, one connected with macrophages polarisation, and four were associated with CVDs, mainly with SMC function and phenotypic switch (NEAT1, MIR100HG, HIF1A-AS3, and MRI29B2CHG). The enrichment analysis detected additional lncRNAs H19, CARMN, FTX, and MEG3 linked with DM. Our study revealed several lncRNAs in diabetic PAD patients associated with the physiological function of SMCs. These lncRNAs might serve as potential therapeutic targets to improve the function of SMCs within the diseased tissue and, thus, the clinical outcome.

Peripheral Arterial Disease and the Diabetic Foot Syndrome: Neuropathy Makes the Difference! A Narrative Review.

Background: In vascular medicine, peripheral arterial disease (PAD) and diabetic foot syndrome (DFS) are often considered synonymous with respect to the need for revascularization. In PAD patients, clinical symptoms reflect the degree of atherosclerotic disease, since peripheral innervation, including pain sensation, is not usually compromised. In DFS patients, however, symptoms of relevant foot ischemia are often absent and progression of ischemia goes unnoticed owing to diabetic polyneuropathy, the loss of nociception being the main trigger for foot ulcers. This review analyzes the fundamental differences between PAD and DFS against the background of polyneuropathy. Methods: The literature research for the 2014 revision of the German evidence-based S3-PAD-guidelines was extended to 2023. Results: Vascular examination is imperative for both, PAD and DFS. Stage-dependent revascularization is of utmost importance in PAD patients, especially those suffering from critical limb-threatening ischemia (CLTI). Successful therapy of DFS goes further, including infection and metabolic control, wound management, offloading the foot and lifelong prophylaxis in the course of a multidisciplinary treatment concept. Revascularization is not needed in all cases of DFS. Conclusions: There are fundamental differences between PAD and DFS with respect to pathophysiology, the anatomical distribution of arterial occlusive processes, the clinical symptoms, the value of diagnostic tools such as the ankle-brachial index, and classification. Also, therapeutic concepts differ substantially between the two patient populations.

Oxidative damage in the gastrocnemius predicts long-term survival in patients with peripheral artery disease

Patients with peripheral artery disease (PAD) have increased mortality rates and a myopathy in their affected legs which is characterized by increased oxidative damage, reduced antioxidant enzymatic activity and defective mitochondrial bioenergetics. This study evaluated the hypothesis that increased levels of oxidative damage in gastrocnemius biopsies from patients with PAD predict long-term mortality rates. Oxidative damage was quantified as carbonyl adducts in myofibers of the gastrocnemius of PAD patients. The oxidative stress data were grouped into tertiles and the 5-year, all-cause mortality for each tertile was determined by Kaplan-Meier curves and compared by the Modified Peto test. A Cox-regression model was used to control the effects of clinical characteristics. Results were adjusted for age, sex, race, body mass index, ankle-brachial index, smoking, physical activity, and comorbidities. Of the 240 study participants, 99 died during a mean follow up of 37.8 months. Patients in the highest tertile of oxidative damage demonstrated the highest 5-year mortality rate. The mortality hazard ratios (HR) from the Cox analysis were statistically significant for oxidative damage (lowest vs middle tertile; HR = 6.33; p = 0.0001 and lowest vs highest; HR = 8.37; p < 0.0001). Survival analysis of a contemporaneous population of PAD patients identifies abundance of carbonyl adducts in myofibers of their gastrocnemius as a predictor of mortality rate independently of ankle-brachial index, disease stage and other clinical and myopathy-related covariates.

The Impact of Mental Health on Patient Outcomes in Peripheral Arterial Disease and Critical Limb Threatening Ischemia and Potential Avenues to Treatment

The physical consequences of peripheral arterial disease (PAD) are well established, however, the impact of comorbid mental health disorders such as depression and anxiety are not well understood. The impact of psychological stress is not only associated with worse perioperative morbidity and mortality but also with a physiologic cascade that accelerates plaque formation. Increasing screening to identify and subsequently treat comorbid mental health disorders is an integral next step in improving outcomes in PAD management. Failure to adequately address social and psychological impact on PAD patients will further widen the gap in disparities faced by high risk and disenfranchised populations. Integration of mental health professionals, addiction specialists, and community navigators into multidisciplinary care teams can bolster support for PAD patients and improve outcomes.

Educating Trainees to Treat Peripheral Arterial Disease: Challenges and Opportunities

Educating trainees to treat Peripheral Artery Disease (PAD) carries specific contemporary challenges. The national increase of the prevalence of PAD combined with a significant shortage of vascular surgeons creates a need for concern for future management of this complex disease. Over the past two decades, traditional (5+2) and integrated (0+5) paradigms have fostered trainee annual growth and comparable case distribution and volumes in endovascular and open surgical treatment options have been maintained. Close evaluation into not only the absolute numbers of surgical cases, but the level of trainee involvement in each logged case is recommended. Future implementation of the Entrustable Professional Activity (EPA) modules will hopefully assist in ensuring linear development of surgical skill and judgement. Additionally, advances in individual and systems level techniques to enhance skill acquisition in the form of “off-the job training” and simulation-based training may provide an enhancement to traditional technical training methods. Finally, the possibility and role of Artificial Intelligence in vascular surgery skill training must not be ignored, but carefully explored and utilized to modernize cognitive and technical skill preparation for trainees in the and delivery of care for PAD patients. Overall, the training residents for the treatment of PAD patients will be associated with new challenges that vascular surgery must embrace and surmount to advance our specialty.

Convolutional Neural Networks to Study Contrast-Enhanced Magnetic Resonance Imaging–Based Skeletal Calf Muscle Perfusion in Peripheral Artery Disease

Peripheral artery disease (PAD) is associated with impaired blood flow in the lower extremities and histopathological changes of the skeletal calf muscles resulting in abnormal microvascular perfusion. We studied the use of convolutional neural networks (CNNs) to differentiate PAD patients from matched controls by utilizing perfusion pattern features from contrast-enhanced magnetic resonance imaging (CE-MRI) of the skeletal calf muscles. We acquired CE-MRI based skeletal calf muscle perfusion in 56 individuals (36 PAD patients, 20 matched controls). Microvascular perfusion imaging was performed post reactive hyperemia at the mid-calf level with a temporal resolution of 409 ms. We analyzed perfusion scans up to 2 minutes indexed from the local pre-contrast arrival time frame. Skeletal calf muscles including the anterior muscle (AM), lateral muscle (LM), deep posterior muscle group (DM), and the soleus (SM) and gastrocnemius muscles (GM) were segmented semi-automatically. Segmented muscles were represented as 3D DICOM stacks of CE-MRI perfusion scans for deep learning analysis. We tested several CNN models for the 3D CE-MRI perfusion stacks to classify PAD patients from matched controls. Two of the best performing CNNs (resNet and divNet) were selected to develop the final classification model. A peak accuracy of 75% was obtained for both resNet and divNet. Specificity was 80% and 94% for resNet and divNet, respectively. In conclusion, deep learning utilizing CNNs, and CE-MRI skeletal calf muscle perfusion can discriminate PAD patients from matched controls. Deep learning methods may be of interest for the study of PAD.

Rationale and design for the randomized placebo-controlled double-blind trial studying the effect of single antiplatelet therapy (clopidogrel) versus dual antiplatelet therapy (clopidogrel/acetylsalicylic acid) on the occurrence of atherothrombotic events following lower extremity peripheral transluminal angioplasty (CLEAR-PATH)

RationaleAntiplatelet therapy (APT) is the standard of care after endovascular revascularization (EVR) in patients with peripheral artery disease (PAD). APT aims to prevent both major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Nonetheless, the rates of MACE and MALE after EVR remain high. In coronary artery and cerebrovascular disease, dual APT (DAPT)compared to acetylsalicylic acid alone has proven to reduce MACE without increasing the risk of major bleeding when applied for a restricted number of weeks. However, within the PAD population, insufficient data are available to understand the potential attributable effect of DAPT over single APT (SAPT). Therefore, prospective randomized studies in targeted study populations are warranted. Trial designCLEAR-PATH is a Dutch multicenter, double-blind, placebo-controlled, randomized trial comparing SAPT (clopidogrel 75mg plus placebo) with DAPT (clopidogrel 75mg plus acetylsalicylic acid 80mg) in patients with PAD undergoing EVR. CLEAR-PATH includes a time-to-event analysis with a follow-up of one year. The primary composite efficacy endpoint consists of all-cause mortality, nonfatal stroke, nonfatal myocardial infarction, severe limb ischemia, (indication for) re-intervention due to any symptomatic restenosis, re-occlusion, or due to acute limb ischemia, and major amputation. The primary safety endpoint contains major bleeding following the Thrombolysis In Myocardial Infarction classification. The enrolment started in August 2022. In total 450 primary efficacy outcome events are required which expectedly amounts to 1696 subjects. Recruitment will take approximately 36 months. ConclusionCLEAR-PATH will assess the efficacy and safety of DAPT compared to SAPT following EVR in PAD patients.

Leveraging Artificial Intelligence to Optimize the Care of Peripheral Artery Disease Patients

Peripheral artery disease is a major atherosclerotic disease that is associated with poor outcomes such as limb loss, cardiovascular morbidity, and death. Artificial intelligence has seen increasing integration in medicine, and its various applications can optimize the care of peripheral artery disease patients in diagnosis, predicting patient outcomes, and imaging interpretation. In this review, we introduce various artificial intelligence applications such as natural language processing, supervised machine learning, and deep learning, and we analyze the current literature in which these algorithms have been applied to peripheral artery disease.

High Serum Galectin-3 Level as a Potential Biomarker of Peripheral Artery Disease in Patients Undergoing Hemodialysis

High Serum Galectin-3 Level as a Potential Biomarker of Peripheral Artery Disease in Patients Undergoing Hemodialysis

Exploring Possible Links: Thigh Muscle Mass, Apolipoproteins, and Glucose Metabolism in Peripheral Artery Disease-Insights from a Pilot Sub-Study following Endovascular Treatment.

Peripheral artery disease (PAD) compromises walking and physical activity, which results in further loss of skeletal muscle. The cross-sectional area of the thigh muscle has been shown to be correlated with systemic skeletal muscle volume. In our previous pilot study, we observed an increase in thigh muscle mass following endovascular treatment (EVT) in patients with proximal vascular lesions affecting the aortoiliac and femoropopliteal arteries. Considering the potential interactions between skeletal muscle, lipid profile, and glucose metabolism, we aimed to investigate the relationship between thigh muscle mass and apolipoproteins as well as glucose metabolism in PAD patients undergoing EVT. This study is a prespecified sub-study conducted as part of a pilot study. We prospectively enrolled 22 symptomatic patients with peripheral artery disease (PAD) and above-the-knee lesions, specifically involving the blood vessels supplying the thigh muscle. The mid-thigh muscle area was measured with computed tomography before and 6 months after undergoing EVT. Concurrently, we measured levels of apolipoproteins A1 (Apo A1) and B (Apo B), fasting blood glucose, 2 h post-load blood glucose (using a 75 g oral glucose tolerance test), and glycated hemoglobin A1c (HbA1c). Changes in thigh muscle area (delta muscle area: 2.5 ± 8.1 cm2) did not show significant correlations with changes in Apo A1, Apo B, fasting glucose, 2 h post-oral glucose tolerance test blood glucose, HbA1c, or Rutherford classification. However, among patients who experienced an increase in thigh muscle area following EVT (delta muscle area: 8.41 ± 5.93 cm2), there was a significant increase in Apo A1 (pre: 121.8 ± 15.1 mg/dL, 6 months: 136.5 ± 19.5 mg/dL, p < 0.001), while Apo B remained unchanged (pre: 76.4 ± 19.2 mg/dL, 6 months: 80.5 ± 4.9 mg/dL). Additionally, post-oral glucose tolerance test 2 h blood glucose levels showed a decrease (pre: 189.7 ± 67.5 mg/dL, 6 months: 170.6 ± 69.7 mg/dL, p = 0.075). Patients who exhibited an increase in thigh muscle area demonstrated more favorable metabolic changes compared to those with a decrease in thigh muscle area (delta muscle area: -4.67 ± 2.41 cm2). This pilot sub-study provides insights into the effects of EVT on thigh muscle, apolipoproteins, and glucose metabolism in patients with PAD and above-the-knee lesions. Further studies are warranted to validate these findings and establish their clinical significance. The trial was registered on the University Hospital Medical Information Network Clinical Trials Registry (UMIN000047534).