Peripheral Arterial Disease Patients Research Articles

Abstract 4136687: VTRNA2-1 Promoter Methylation as a Prognostic Biomarker in Peripheral Artery Disease: Implications for Maternal Nutritional Influence

Background: Peripheral artery disease (PAD) is associated with high morbidity and mortality and is closely related to diabetes mellitus (DM) and atherosclerosis. Recent advances in epigenetics have highlighted the critical relationships of non-coding RNA Vault RNA 2-1 (VTRNA2-1) promoter methylation and periconceptional nutritional status. Furthermore, the abundance of methylation of the VTRNA2-1 promoter is associated with glucose metabolism and cell aging. This study investigates the association between VTRNA2-1 promoter methylation and clinical outcomes in PAD patients requiring revascularization. Hypothesis: VTRNA2-1 promoter methylation status is associated with clinical outcomes in PAD patients requiring revascularization. Methods: A total of 133 PAD patients requiring revascularization were enrolled. Inclusion criteria included adults over 20 years old, consent to participate, and a requirement for angioplasty. Blood samples were processed to isolate leukocytes, and DNA was extracted using the DNeasy blood kit. Bisulfite pyrosequencing was performed to quantify CpG site-specific DNA methylation at the VTRNA2-1 promoter locus. General population samples from the National Health Research Institutes were used as the control group to compare the methylation status. Patients' one-year clinical outcomes were evaluated. Results: The study found significant differences in VTRNA2-1 promoter methylation status between PAD patients and the control group (P < 0.001). Hypomethylation of VTRNA2-1 promoter was associated with a higher amputation rate in PAD patients (HR 2.19, 95% CI 1.09-4.42, p=0.027). Among patients without ESRD (N=79), those with hypomethylation had a significantly increased risk of major adverse limb events (MALE) (HR 2.78, 95% CI 1.11-6.97, p=0.024), amputations (HR 2.58, 95% CI 1.02-6.57, p=0.044), and progression to ESRD (p=0.039). Conclusion: The methylation status of VTRNA2-1 promoter is significantly different between PAD patients and the normal population, with hypomethylation linked to poorer clinical outcomes in PAD patients undergoing revascularization. These findings suggest that VTRNA2-1 promoter methylation status could serve as a valuable biomarker for predicting prognosis and guiding treatment strategies in PAD. Our results open a molecular link between the periconceptional environment and the risks of PAD.

Abstract 4129523: MicroRNA-1282 Rescues Diabetic Limb Ischemia Via a SERF2-Protein Aggregation Pathway

Introduction: Patients with diabetes are at higher risk of chronic limb-threatening ischemia (CLTI), a severe form of peripheral artery disease (PAD) causing restricted blood flow to the lower limbs due, in part, to impaired angiogenesis. However, the role of microRNAs (miRNAs) in diabetic CLTI remains poorly understood. By integrating plasma miRNA sequencing data from PAD patients with diabetes with a diabetic CLTI mouse model, we have recently identified the conserved miRNA miR-1282 that is in cis-antisense orientation to SERF2, a gene associated with amyloid aggregation. Therefore, we hypothesize that miR-1282 orchestrates endothelial angiogenesis and proteostasis during diabetic CLTI. Methods: Using miR-1282 overexpression or SERF2 knockdown studies, we characterized mouse orthologs of human miR-1282 and SERF2 for angiogenesis, apoptosis, protein aggregation, and oxidative stress in diabetic mouse skeletal muscle endothelial cells (ECs). In vivo, miR-1282 mimics were delivered intramuscularly to assess their impact on blood flow recovery, angiogenesis, and protein aggregation. Mechanistic insights in ECs were gained via RNA-seq, predictive algorithms, and proteomic analyses. Results: miR-1282 inhibited the expression of its cis-antisense target SERF2 by 98%. miR-1282 is a hypoxia-induced endothelial-enriched miRNA, and its expression was inversely correlated with SERF2 expression. miR-1282 levels were markedly reduced after femoral artery ligation (FAL) in diabetic db/db mice. Overexpression of miR-1282 or SERF2 knockdown enhanced angiogenesis and reduced protein aggregation, apoptosis, and oxidative stress in both normal and hypoxic conditions in vitro. Delivery of miR-1282 mimics in db/db mice improved blood flow recovery by 108% and angiogenesis by 98%, and reduced protein aggregation by 48% and tissue necrosis. Coupling RNA-seq profiling and prediction algorithms of ECs upon miR-1282 overexpression or SERF2 knockdown revealed EREG, BAG5, CASP3, ARG1, and HSP90AA1 as potential downstream regulators. Pathway enrichment analysis implicated inhibition of endothelial apoptosis, ER stress, and protein stability among the most dysregulated processes. Conclusion: A novel mouse ortholog of human miR-1282 augments endothelial functions and diminishes protein aggregation in diabetic CLTI via suppression of its cis-antisense target SERF2. These findings uncover new potential therapeutic targets in treating diabetic CLTI.

Abstract 4132769: Carnosine Supplementation Improves Walking Ability of Peripheral Arterial Disease Patients

Introduction: Peripheral artery disease (PAD) is a significant cause of cardiovascular morbidity and mortality, characterized by atherosclerosis in the skeletal muscle. Currently no mechanism-based therapeutics are available for this diseased population. In the muscle, histidyl dipeptides, such as carnosine (ranging between 5-10 mM) possess the abilities to bind with toxic lipid peroxidation products, such as acrolein. Preclincial studies show carnosine is depleted in the ischemic leg, increasing intramuscular carnosine improves angiogenesis, and blood flow in the ischemic leg. In humans, carnosine levels are increased in the muscle with carnosine supplementation. However, little is known whether carnosine levels are affected in PAD patients and its effect on their walking ability. Hypothesis: Carnosine supplementation will improve walking ability of PAD patients. Methods: We recruited normal (males: n=48; females: n=52; age: 50 ±10 years) and PAD subjects (males: n=52; females: n=41; age: 67±8 years; ankle brachial index (ABI): 0.65±0.18 measured urinary histidyl dipeptides, histidyl dipeptide-aldehyde conjugates, and oxidative stress markers: N-Acetyl-S-(3-hydroxypropyl)-L-Cysteine (3-HPMA) and N-acetyl-S-(2-carboxyethyl)-L-cysteine (CEMA), both are acrolein metabolites. PAD subjects (n=7; n=5 females and n=2 males; ABI: 0.68±0.08, age: 63±8 years) were supplemented with carnosine 2 g/day for 3 months, measured distance covered in a six-minute walk test (6MWT), ABI, blood profile at baseline and after completion. Results: In PAD subjects urinary carnosine was decreased (normal: 20±29 vs PAD:11±14 nmoles/mg creatinine, p<0.024), carnosine aldehdye conjugates were increased (carnosine propanal: 1.46±1.27 vs normal 0.56±1.08 nmoles/mg creatinine, p<0.0001; and carnosine propanol: 4.66±2.80 vs normal 1.52±1.21 nmoles/mg creatinine, p<0.0001). Oxidative stress markers were increased in the PAD subjects (CEMA: 341±210 vs normal: 119±86 ng/mg creatinine, p<0.0004 and 3HPMA: 6.57±6.32 ng/mg protien vs normal: 5.49±5.28 ng/mg creatinine, p<0.001). Following carnosine supplementation, blood profile was unchanged. Distance covered in 6MWT increased by 166±204 feet (before: 577±129 vs 743±152 feet after, p<0.048) and there was an increasing trend in ABI (before: 0.68±0.08 vs 0.80±0.19; after, p<0.18). Conclusion: Urinary carnosine could serve as a biomarker to evaluate PAD pathology and carnosine supplementation may improve walking ability of PAD patients.

Abstract 4127909: Smartphone-enabled, home-based exercise in patients with symptomatic peripheral arterial disease: the Smart Step Grady randomized trial

Introduction: About 10% of peripheral artery disease (PAD) patients develop claudication, with African Americans at higher risk and more severe symptoms. While supervised exercise therapy (SET) is a primary treatment, its uptake is low. We assessed the feasibility and effectiveness of smartphone-delivered home-based exercise therapy (HBET) in improving functional capacity and PAD symptoms in low-resource settings lacking SET. Methods: We conducted an interim analysis of Smart Step, a pilot randomized trial (1:1 ratio) comparing smartphone-enabled HBET to usual care (UC) in symptomatic PAD patients at Grady Memorial Hospital, a public safety net hospital in Atlanta, GA, from August 2018 to March 2024. The HBET group received virtual exercise coaching, app-based education, messaging, and reminders for 12 weeks. The primary outcome was the change in 6-minute walking distance (6MWD) at 12 weeks. Secondary outcomes included changes in the Walking Impairment Questionnaire (WIQ) and Short Form 36 (SF-36) scores. Data were analyzed using intention-to-treat, with mixed model repeated measures regression assessing the association between 6MWD and treatment. Results: We screened 102 patients and enrolled 46. To date, 26 (56%) participants have completed the study, 6 (13%) dropped out, and 14 (30%) are pending completion. The mean [SD] age was 63 [12] years, with 50% female and 90% African American. After 12 weeks, the mean 6MWD increased by 15.7 m from a baseline of 336.0 m in the HBET arm (n=13) and decreased by 6.6 from a baseline of 310.2 m in the UC arm (n=13). The between-group difference was 22.4 [95% CI -11.8 – 56.6] m; p=0.19). The WIQ stair climbing score changed by -10.9 in the UC arm vs. 7.1 in the HBET arm (between group difference 17.9 [95% CI 1.1-34.8]; p=0.04), while the other WIQ sub-scores were more similar between groups. The 12-week changes in SF-36 scores were not different by group. Conclusion: In this preliminary analysis, the HBET arm showed within-group improvements in 6MWD and symptoms after 12 weeks, but most changes were not significantly different when comparing them with the UC arm. Future analyses are pending and will provide the necessary statistical power for a more precise measure of the treatment effects.

Abstract 4139141: Predicted efficacy of inclisiran on cardiovascular outcomes in lower extremity peripheral artery disease: results of the In Silico Sirius study

Introduction: Symptomatic lower extremity peripheral artery disease (PAD) patients have the highest risk of cardiovascular (CV) outcomes among patients with established atherosclerotic cardiovascular disease (ASCVD). Inclisiran, an siRNA targeting PCSK9 mRNA, reduces LDL-C levels. In SIRIUS in silico trial (NCT05974345), inclisiran was predicted to lower CV events in ASCVD patients. Research question/Hypothesis: SIRIUS in silico study aims to predict the efficacy of inclisiran on CV outcomes in subgroups of patients with or without PAD. Methods: The SIRIUS in silico trial was conducted using a knowledge-based mechanistic computational model of ASCVD applied to a virtual ASCVD population with LDL-C ≥ 70 mg/dL. Each virtual patient is its own control. This model was previously calibrated and validated before running the trial. SIRIUS compared the efficacy of inclisiran vs placebo on top of High Intensity (HI) statins with or without ezetimibe on 3-Point-MACE defined as a composite of time to first occurrence of CV death, nonfatal myocardial infarction (MI) or nonfatal ischemic stroke (IS) over 5 years. Occurrence of major acute limb events (MALE) was also individually assessed in time-to-first-event analyses. Results: Among 204, 691 virtual SIRIUS ASCVD patients, 28,072 (13.7%) had PAD. At 5 years, the mean predicted percentage reduction in LDL-C with inclisiran as compared to placebo was -49.3% and -49.8% in patients with or without PAD, respectively. The predicted rate of 3P-MACE in the inclisiran arm was consistently lower than in the placebo arm in patients with PAD (17.62% vs 22.88%; Hazard Ratio (HR): 0.75 medium uncertainty) and in patients without PAD (10.33% vs 13.64%; HR: 0.75 low uncertainty). Compared to placebo, inclisiran was also predicted to consistently reduce MALE in patients with or without PAD (2.71% vs 4.11%; HR: 0.65 medium uncertainty and 0.19% vs 0.29%; HR: 0.66 high uncertainty respectively). Conclusion: Pending the results of ORION-4 and VICTORION-2-P, this first In Silico trial in virtual PAD patients predicted a potential effect of inclisiran on 3P-MACE and MALE reductions over 5 years follow-up.

An association between the blood perfusion parameters in foot tissues and the severity of arterial occlusion and stenosis in the lower extremities

Rationale: Peripheral artery disease (PAD) is common among the elderly and increases the risk of cardiovascular events, disability and death. PAD course and outcomes depend not only on the condition of macrovasculature but also on the tissue perfusion. We have previously shown that Type 2 diabetic patients with lower extremity ischemia have significantly lower perfusion than healthy volunteers, and the ratio of basal perfusion in the arm and leg (BP1/BP3) measured by incoherent optical fluctuation flowmetry (IOFF) allows to identify hemodynamically significant stenoses. Aim: To analyze associations between perfusion parameters registered by IOFF and the severity of vascular involvement in PAD patients. Methods: This single center cross-sectional study included 38 PAD patients admitted to the Department of Vascular Surgery and Coronary Artery Disease. The arteries were assessed with duplex Doppler ultrasonography (DDU), according to the results of which the PAD severity score and ankle-brachial index (ABI) were calculated. Skin microhemodynamic parameters were recorded by IOFF. The basal perfusion on the arm (BP1), the dorsal foot surface and the toe (BP2 and BP3), the ratio BP1/BP3, local thermal hyperemia (LTH2 and LTH3) and an increase in perfusion after heating on two leg zones (LTH2-BP2, LTH3-BP3) were evaluated and expressed in perfusion units (PU). BP1, BP3, and BP1/BP3 values were additionally measured with laser Doppler flowmetry (LDF). The analysis was performed depending on the degree of arterial involvement determined by DDU for each limb separately (n = 73). There were ≥ 50% stenoses in 15 extremities (Group 1), occlusion of one of the major arteries in 42 (Group 2) and ≥ 2 occlusions in 16 lower extremities (Group 3). Results: In the groups 1, 2 and 3, the values of most parameters estimated by IOFF decreased with an increase in severity of limb lesions. As an example, the respective perfusion parameters for the big toe in the study groups were as follows: BP3 4.0 [2.0; 9.8], 2.2 [0.9; 3.7] and 1.1 [0.7; 2.6] PU (p = 0.007); LTH3 10.0 [6.4; 14.9], 5.0 [1.5; 7.8] and 2.5 [1.4; 4.5] PU (p 0.001), and LTH3-BP3 3.8 [2.6; 7.8], 2.4 [0.6; 4.3] and 1.2 [0.4; 1.5] PU (p = 0.001). The BP1/BP3 ratio in the above mentioned group increased: 1.8 [0.8; 7.7], 7.2 [3.4; 21.3] and 14.2 [6.6; 18.3] (p = 0.004), respectively. No similar trend was found for this parameter registered by LDF. There were significant correlations between the lower extremities perfusion parameters measured by IOFF and ABI, with the correlation coefficients ranging from 0.365 to 0.717 (p 0.05). Conclusion: The functional parameters of the skin microhemodynamics vary with different PAD severity. In addition, they correlate with clinical indicators of atherosclerosis. The IOFF technique can be promising as an additional quantitative method for assessment of microvascular blood flow in patients with PAD.

Risk-Prediction Model of Restenosis after Endovascular Treatment for Peripheral Arterial Disease: A Systematic Review and Meta-analysis.

Peripheral artery disease (PAD) patients after endovascular treatment (EVT) have a relatively high restenosis rate. However, this risk can be mitigated through precise risk assessment and individualized self-management intervention plans. Moreover, the number of predictive models for restenosis risk in PAD patients after EVT is gradually increasing, yet these results of study exhibit certain discrepancies, raising uncertainties regarding the quality and applicability in clinical practice and future research. The objective of this study was to systematically evaluate risk-predictive models for restenosis in patients with PAD after EVT. A systematic review and meta-analysis of predictive model construction and validation using observational studies was undertaken. The China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, SinoMed, PubMed, Web of Science, Embase, and the Cochrane Library were searched from inception to January 1, 2024. Two researchers independently conducted literature screening and data extraction, encompassing study design, data sources, outcome definition, sample size, predictive factors, model development, and performance. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was used for risk of bias and applicability assessment of the models. A total of 4275 studies were retrieved, ultimately resulting in the inclusion of 7 articles comprising 7 predictive models for restenosis in PAD patients after EVT, with a restenosis incidence ranging from 21.8% to 39.7%. The total sample size of the included models ranged from 137 to 1578 cases, with logistic regression analysis being the most commonly used modeling method. All models were built using R software. Only 2 models underwent external validation, and the reported area under the curve ranged from 0.728 to 0.864. The summary area-under-the-curve statistic was 0.80 (95% confidence interval [CI], 0.74-0.86), with an approximate prediction interval of 0.80 (95% CI, 0.62-0.91) . The number of included predictive factors ranged from 3 to 10, with the most common factors being age, Trans-Atlantic Inter-Society Consensus Ⅱ classification, hypertension, diabetes, high-sensitivity C-reactive protein, and surgical approach. All studies exhibited high risk of bias, primarily attributed to inappropriate sources of data and poor reporting of the analysis domain. Predictive models for restenosis after EVT in PAD patients demonstrate overall good predictive performance but are still in the developmental stage with higher risk of bias. Future studies should follow the TRIPOD statement, focusing on the development of new models with larger samples, rigorous study designs, and multicenter external validation. This systematic review adheres to the PRISMA 2020 statement, offering the most recent systematic assessment of risk prediction models for restenosis following endovascular treatment in peripheral arterial disease.The newly developed PROBAST tool was employed to assess the risk of bias and the applicability of the existing evidence.This review emphasizes the practical utility, limitations of the current evidence, and recommendations for future research, with the goal of providing valuable information for clinicians and patients in their decision-making process, while also supporting the advancement of future research endeavors.

Etrinabdione (VCE-004.8), a B55α activator, promotes angiogenesis and arteriogenesis in critical limb ischemia

BackgroundVasculogenic therapies explored for the treatment of peripheral artery disease (PAD) have encountered minimal success in clinical trials. Addressing this, B55α, an isoform of protein phosphatase 2A (PP2A), emerges as pivotal in vessel remodeling through activation of hypoxia-inducible factor 1α (HIF-1α). This study delves into the pharmacological profile of VCE-004.8 (Etrinabdione) and evaluates its efficacy in a preclinical model of critical limb ischemia, with a focus on its potential as a PP2A/B55α activator to induce angiogenesis and arteriogenesis.MethodsVascular endothelial cells were used for in vitro experiments. Aorta ring assay was performed to explore sprouting activity. Matrigel plug-in assay was used to assess the angiogenic potential. Critical limb ischemia (CLI) in mice was induced by double ligation in the femoral arteria. Endothelial vascular and fibrotic biomarkers were studied by immunohistochemistry and qPCR. Arteriogenesis was investigated by microvascular casting and micro-CT. Proteomic analysis in vascular tissues was analyzed by LC–MS/MS. Ex-vivo expression of B55α and biomarkers were investigated in artery samples from PAD patients.ResultsVCE-004.8 exhibited the ability to induce B55α expression and activate the intersecting pathways B55α/AMPK/Sirtuin 1/eNOS and B55α/PHD2/HIF-1α. VCE-004.8 prevented OxLDL and H2O2-induced cytotoxicity, senescence, and inflammation in endothelial cells. Oral VCE-004.8 increased aorta sprouting in vitro and angiogenesis in vivo. In CLI mice VCE-004.8 improved collateral vessel formation and induced endothelial cells proliferation, angiogenic gene expression and prevented fibrosis. The expression of B55α, Caveolin 1 and Sirtuin-1 is reduced in arteries from CLI mice and PAD patient, and the expression of these markers was restored in mice treated with VCE-004.8.ConclusionsThe findings presented in this study indicate that Etrinabdione holds promise in mitigating endothelial cell damage and senescence, while concurrently fostering arteriogenesis and angiogenesis. These observations position Etrinabdione as a compelling candidate for the treatment of PAD, and potentially other cardiovascular disorders.

Impact of BMI on Recovery and Quality of Life Post-Revascularization in Peripheral Arterial Disease Patients

Impact of BMI on Recovery and Quality of Life Post-Revascularization in Peripheral Arterial Disease Patients

Machine Learning in Vascular Medicine: Optimizing Clinical Strategies for Peripheral Artery Disease

Abstract Purpose of Review Peripheral Artery Disease (PAD), a condition affecting millions of patients, is often underdiagnosed due to a lack of symptoms in the early stages and management can be complex given differences in genetic and phenotypic characteristics. This review aims to provide readers with an update on the utility of machine learning (ML) in the management of PAD. Recent Findings Recent research leveraging electronic health record (EHR) data and ML algorithms have demonstrated significant advances in the potential use of automated systems, namely artificial intelligence (AI), to accurately identify patients who might benefit from further PAD screening. Additionally, deep learning algorithms can be used on imaging data to assist in PAD diagnosis and automate clinical risk stratification. ML models can predict major adverse cardiovascular events (MACE) and major adverse limb events (MALE) with considerable accuracy, with many studies also demonstrating the ability to more accurately risk stratify patients for deleterious outcomes after surgical intervention. These predictions can assist physicians in developing more patient-centric treatment plans and allow for earlier, more aggressive management of modifiable risk-factors in high-risk patients. The use of proteomic biomarkers in ML models offers a valuable addition to traditional screening and stratification paradigms, though clinical utility may be limited by cost and accessibility. Summary The application of AI to the care of PAD patients may enable earlier diagnosis and more accurate risk stratification, leveraging readily available EHR and imaging data, and there is a burgeoning interest in incorporating biological data for further refinement. Thus, the promise of precision PAD care grows closer. Future research should focus on validating these models via real-world integration into clinical practice and prospective evaluation of the impact of this new care paradigm.

Improving peripheral artery disease screening and treatment: a screening, diagnosis, and treatment tool for use across multiple care settings.

Peripheral artery disease (PAD) is an atherosclerotic disease that contributes to significant morbidity and mortality, including loss of limb, myocardial infarction (MI), stroke, and death. Treatment options are often underutilized. A major limiting factor in PAD care is the ability to efficiently identify and screen at-risk patients. A PAD patient screening and clinician decision support tool was created to improve access to high-quality, evidence-based care to drive improved clinical outcomes. The tool identifies known PAD risk factors and presenting symptoms, in combination with objective data obtained via the ankle-brachial index (ABI). The tool utilizes this data to drive PAD diagnosis, risk assessment, and treatment, and it is adaptable across multiple care settings, by varied health professions. The implementation of a PAD screening and treatment toolkit enhances anticoagulation and PAD stewardship, and it has been integrated into use across various care settings.

Evaluating the connection between mean platelet volume (MPV) and peripheral arterial disease risk: a meta-analysis

Background: Numerous studies have been conducted to evaluate the role of Mean Platelet Volume (MPV) in relation to Peripheral Artery Disease (PAD). However, the results of these studies have been inconsistent regarding the significance of MPV as an indicator for PAD. Objective: This meta-analysis aimed to clarify the role of MPV in PAD by collecting and analyzing data from various studies. The goal was to provide a more definitive assessment of whether MPV levels could serve as a reliable indicator for PAD Methods: We conducted a meta-analysis from July to August 2024, utilizing data from three major databases: Scopus, Embase, and PubMed. We gathered data on MPV levels from studies comparing PAD patients with control groups. The meta-analysis included cumulative effect estimates, with analysis performed using the inverse variance method to synthesize data and evaluate the overall effect of MPV on PAD. Results: Nine studies were included in this meta-analysis, comprising 1,214 PAD cases and 6,568 controls. Our analysis demonstrated that MPV was a significant marker in PAD, with PAD patients having higher MPV levels compared to controls (MD: 0.46; 95%CI: 0.25, 0.66; p Egger: 0.0911; p Heterogeneity <0.0001; p <0.0001). Conclusion: Our findings support that MPV is an important indicator in the context of PAD. Further study is needed to explore the clinical applications of MPV in PAD and to establish standardized thresholds for its use in clinical practice. Keyword: diagnosis, mean platelet volume, peripheral disease, predictor

National dispensing of evidence-based treatment for New Zealand patients before and after peripheral arterial or percutaneous coronary procedures; undertreatment in plain sight

Abstract Background/Introduction Cardiovascular management guidelines recommend that those undergoing arterial procedures for atherosclerotic disease should be on a long-term antithrombotic agent, statin and blood pressure (BP) lowering (triple therapy) to prevent or delay future ischaemic events or death. Internationally, treatment gaps have been reported for people having peripheral arterial disease (PAD) procedures. Purpose We aimed to investigate national rates of triple therapy dispensing before and after admission for a percutaneous coronary intervention (PCI) compared to a PAD procedure. Methods All people aged 18-84 years admitted for a publicly-funded PCI or PAD procedure in New Zealand between 1 January 2015 and 30 June 2020 were identified. Data were linked to national community dispensing records for antithrombotic agents, statins and BP lowering and the adjusted relative risk (adjRR) of dispensing individual medication classes and triple therapy investigated 6 months prior-procedure and 0-6 months and 7-12 months post-procedure. Analyses were controlled for age, sex, prioritised ethnicity, socioeconomic deprivation index, diabetes and prior cardiovascular disease. Results During the study period, 26,383 people were admitted for a PCI procedure and 10,938 people for PAD. Compared to PCI, those with PAD were more likely to be women, older (median age 69 vs 66 years), of Māori or Pacific ethnicity, living in more deprived communities, more likely to have diabetes (33% vs 24%) and a prior admission for cardiovascular disease (63% vs 52%). Triple therapy in the 6 months prior to procedure was 48% for PAD compared to 37% for PCI (adjRR 1.04; 1.03-1.05); however, in the 6 months post-discharge, improved for PCI more than PAD (PAD 58% vs PCI 91%, [adjRR 0.82; 0.81-0,83]) with decreased dispensing in both cohorts by 7-12 months post procedure (PAD 55% vs PCI 83%, [adjRR 0.84; 0.83-0,84]). Conclusions Patients undergoing atherosclerotic arterial procedures are at high risk of future fatal and nonfatal cardiovascular events. Less than half the patients who were admitted for a PCI or PAD procedure had been dispensed triple therapy in the 6 months prior to admission. Post procedure, 91% of PCI patients were on triple therapy but this substantial increase did not occur for PAD patients. The risk management gap for those who have peripheral arterial compared to coronary procedures indicates clear clinical and system-related deficiencies and a national quality improvement approach is required to address these issues. Figure 1. Adjusted relative risk of being dispensed preventive medications for patients who had a PAD procedure, compared to patients who had a PCI procedure [after adjusting for age, sex, ethnicity, NZDep, history of CHD (including prior PCI and CABG), stroke/TIA, haemorrhagic stroke, heart failure, PVD, and diabetes]

Comparison of Early Outcomes in Patients Who Underwent Common Femoral Thromboendarterectomy with Vein versus Bovine Pericardial Patches

The treatment outcomesof vein and bovine pericardial patches in thromboendarterectomy (TEA) for common femoral artery (CFA) lesions in patients with peripheral arterial disease (PAD) remain unclear. The purpose of this study was to evaluate the efficacy and safety of the bovine pericardial patch by comparing it with vein patch angioplasty. This was a multicenter retrospective study. We reviewed the data of patients who underwent TEA with patch angioplasty (vein versus bovine pericardial patch angioplasty) for PAD between January 2018 and December 2022. Indication for revascularization is PAD patients with claudication symptoms to rest pain and foot ulcers that interfere with daily life, with lesions in the CFA region. The primary endpoint was 2-year patency. The secondary endpoints were postoperative wound complications, including patch rupture, and safety of remote-phase puncture of the patch area after patch angioplasty. Within the observation period, TEA was performed on 157 limbs in 136 patients using vein patches, and on 86 limbs in 79 patients using bovine pericardial patches. The number of claudication/rest pain/tissue loss was 110/13/34 cases in the vein patch group and 57/14/15 cases in the bovine pericardial patch group, respectively. No significant differences were observed in patient characteristics. No significant between group differences were observed in operative time, blood loss, or percentage of patients who underwent concomitant revascularization during the procedure. The 2-year primary patency rates of the vein and bovine pericardial patch were 95.6% and 92.8%, respectively (P= .49). The rate of surgical site infection (SSI) in this study was 2.5% in the vein patch group and 5.8% in the bovine pericardial patch group, respectively (P=.29). Rupture of the patch occurred in 4 (2.5%) and 4 (4.7%) patients in the vein and bovine pericardial patch groups, respectively (P= .46), and the percentage of cases requiring revision of the patch site was 7 (4.5%) and 5 (5.8%) in the vein and bovine pericardial patch groups, respectively (P= .76). Postoperatively, 23 patients in the vein and 13 patients in the bovine pericardial patch groups underwent patch puncture during the remote period. The median follow-up duration from the date of the surgery to the date of the puncture was 544 days and 374 days in the vein and bovine pericardial patch groups, respectively. No patch-related complications were observed during remote stage puncture. Compared with vein patches, TEA with bovine pericardial patches had acceptable outcomes in terms of patency and postoperative complications.

Safety and Efficacy of Home-Based Walking Exercise for Peripheral Artery Disease

IntroductionHome-based walking exercise is first-line therapy for peripheral artery disease (PAD), but benefits of home-based walking exercise are variable. This study evaluated whether specific clinical characteristics were associated with greater improvement after home-based walking exercise or with higher rates of serious adverse events (SAEs). MethodsData were combined from two randomized clinical trials comparing home-based walking exercise to control in PAD. The home-based exercise interventions used behavioral interventions to help participants adhere to exercise. The primary outcome was the proportion of PAD participants who improved 6-minute walk (6MW) by at least 20 meters. Serious adverse events consisted of overnight hospitalizations or death that occurred during the randomized clinical trial. ResultsOf 376 PAD participants [69.6 years, 54.5% Black, 49.5% women], 217 were randomized to exercise and 159 to control. Home-based exercise improved 6MW by at least 20 meters in 100 (54.9%) participants, compared to 37 (28.0%) in control (Odds Ratio 3.13 (95% CI: 1.94,5.06), P< 0.001. Age, sex, race, comorbidities, baseline 6MW, and income did not significantly alter the effect of home-based exercise on improved 6MW. SAEs occurred in 28.1% and 23.3% of participants randomized to exercise and control, respectively (p=0.29). There were statistically significant interactions, indicating that home-based exercise increased SAE rates, compared to control, in Black compared to non-Black participants (P interaction <0.001), in those with vs. without coronary artery disease (CAD) (P interaction<0.001), and in people with vs. without history of heart failure (P interaction=0.005). ConclusionAmong people with PAD, home-based exercise improved 6MW by at least 20 meters in 54.9% of people. Older age, female sex, Black race, and specific comorbidities were not associated with lower rates of attaining meaningful improvement in 6MW following home-based exercise. Further study is needed to establish whether certain patient characteristics, such as history of coronary artery disease, may affect SAE rates in PAD patients participating in home-based exercise.

Temporal Trends and Mortality Patterns in Peripheral Arterial Disease: A Comprehensive Analysis of Hospitalized Patients in Kazakhstan between 2014 and 2021.

Peripheral artery disease (PAD) is a global health concern associated with arterial narrowing or blockage, leading to significant morbidity and mortality. The aim of this study is to assess the disease burden and trends in mortality utilizing nationwide administrative health data. This retrospective study utilized data from the Unified National Electronic Healthcare System (UNEHS) from 2014 to 2021. Patients meeting PAD criteria were included, with demographic and clinical data analyzed. Cox regression and Competing Risk Analysis assessed mortality risks. Between 2014 and 2021, 19,507 individuals were hospitalized due to PAD, with 8,332 (43%) being women and 11,175 (57%) men. The incidence of PAD increased markedly over the observation period, rising from 79 individuals per million population (PMP) in 2014 to 309 PMP in 2021. Concurrent heart failure (HF), acute myocardial infarction (AMI), diabetes, and essential hypertension were prevalent in 50%, 27%, 27%, and 26% of the PAD patients, respectively. Competing Risk Analysis showed a subdistribution hazard ratio (SHR) of 6.53 [95% CI: 4.65-9.19] for individuals over 80 years. Heart failure was associated with lower all-cause HR [0.80, 95% CI: 0.76-0.86, p < 0.001] but higher SHR [1.30, 95% CI: 1.18-1.44, p < 0.001]. Comorbidities such as heart failure, stroke, and acute myocardial infarction significantly increased mortality risks, while essential hypertension was associated with lower risk of death. The significant rise in the incidence rate of PAD underscores the growing burden of the disease, highlighting the urgent need for targeted preventive and management strategies in Kazakhstan.

Mesenchymal stromal cell therapy (REGENACIP®), a promising treatment option in chronic limb threatening ischemia - a narrative review.

Chronic Limb Threatening Ischemia (CLTI) is a challenging clinical problem associated with high morbidity and mortality. Endovascular interventions have been the cornerstone of treatment whenever possible. It is estimated that CLTI represents < 10% of all Peripheral Artery Disease patients, yet 50% of the patients end up either with a major amputation of the lower limbs or die of cardiovascular causes within one year period, especially in those with unsuccessful revascularization or "no-option" CLTI. Cell-based therapeutics, especially bone marrow-derived mesenchymal stromal cells have emerged as a potential, promising, and novel alternate therapeutic modality in the management of CLTI, bolstered with positive results in numerous research, including randomized and nonrandomized trials. REGENACIP® is one such BM-MSC therapy approved by Central Drugs Standard Control Organization in India for the management of "no-option" Atherosclerotic Peripheral Arterial disease / Buerger's disease patients with established critical limb ischemia in Rutherford Grade III-5 or III-6, not eligible for or have failed traditional revascularization treatment, with rest pain and / or ulcers in the affected limb. The current review aims to deliberate upon the various aspects of CLTI and clinical benefits of REGENACIP® therein.

Aachen smoking cessation and harm reduction (ASCHR) trial study protocol – scientific evaluation of a psychological-telemedical counseling concept for smoking cessation in patients with vascular diseases

BackgroundSmoking is a major risk factor of cardiovascular diseases, notably peripheral arterial disease (PAD). Despite this link, research on smoking cessation interventions in PAD patients remains scarce and inconclusive regarding the efficacy of such interventions.Therefore, elucidating it is crucial and should address both individuals who smoke that are motivated to quit and individuals who smoke heavily lacking the motivation to quit.Methods/DesignThe Aachen Smoking Cessation and Harm Reduction (ASCHR) trial is a prospective randomized controlled study (RCT) on the benefits of telemedical-psychological support for smoking cessation in patients with PAD, funded by the “Innovation Fund” of the Joint Federal Committee in Germany. This trial aims to scientifically assess the efficacy, feasibility, acceptance, and efficiency of a multi-stage smoking cessation program based on the recommendations of the German guideline for smoking cessation tailored to patients with PAD, compared to a control group receiving no intervention. Central to the program is psychological counseling utilizing motivational interviewing techniques, delivered through telemedicine via video consultations. The primary endpoint of the ASCHR trial is the smoking cessation rate after 8 months of intervention, with a secondary endpoint evaluating sustained abstinence at a further 6 months follow-up. Smoking cessation is defined as a carbon monoxide level in exhaled air of less than 6 ppm. We hypothesize that the group receiving the multi-stage cessation program will yield a cessation rate at least 10 percentage points higher than that of usual care. Anticipating a dropout rate of around 35%, the planned sample size is at least N = 1032 study participants.DiscussionShould the trial demonstrate significant positive outcomes, efforts should be made to integrate the program into routine care in Germany, potentially offering a promising base for future smoking cessation support among PAD patients.

TCT-705 Comparative Outcomes of Endovascular Intervention Versus Bypass Surgery for Peripheral Artery Disease in Patients With Atrial Fibrillation: A Retrospective Analysis of the National Inpatient Sample

TCT-705 Comparative Outcomes of Endovascular Intervention Versus Bypass Surgery for Peripheral Artery Disease in Patients With Atrial Fibrillation: A Retrospective Analysis of the National Inpatient Sample

Outcome of Peripheral Arterial Disease in Patients with ESKD on Hemodialysis

Outcome of Peripheral Arterial Disease in Patients with ESKD on Hemodialysis