Explore the vast range of titles available.

Purpose of review Peripheral arterial disease (PAD) is a complex atherosclerotic arterial disease with significant morbidity and mortality. Hence, the role of evidence-based medical therapy in PAD is critical, especially the use of antithrombotic therapy. Recent findings Multiple randomized controlled trials, especially those from the last few years, including but not limited to the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial and the Vascular Outcomes Study of Aspirin along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD (VOYAGER PAD) trial, have shown the utility of the use of various antiplatelet and oral anticoagulant therapies, especially the combination of low-dose rivaroxaban and aspirin, in patients with PAD both with and without revascularization. Summary In this review, we will (i) summarize the current guidelines outlining the evidence-based use of various antithrombotic agents in PAD, (ii) summarize the current available trials supporting such guidelines, and (iii) discuss future trial designs.

Chronic kidney disease (CKD) is a clinical condition characterized by high morbidity and mortality. Globally, CKD is also increasing in prevalence and incidence. The two principal kidney measures namely estimated glomerular filtration rate (eGFR) and albuminuria have been found to be predictors of renal and cardiovascular (CV) endpoints including peripheral artery disease (PAD). The prevalence of PAD was increased in CKD patients and, particularly, in patients with more severe CKD stages. Despite the fact that revascularization strategies are suitable in CKD patients in similar fashion to non-CKD patients, few CKD patients underwent these procedures. In fact, if it is true that revascularization improves prognosis in PAD patients irrespective of baseline eGFR, it was also demonstrated that CKD patients, who underwent revascularization, were at higher risk for amputations, mortality, reintervention and perioperative complications. With the present review article, we have examined the association between CKD, PAD and peripheral revascularization highlighting data about epidemiology, pathophysiologic mechanisms, and results from previous observational and intervention studies. We have also examined the future perspectives and challenges of research around the association between CKD and PAD. Keywords: chronic kidney disease, CKD, peripheral artery disease, PAD, ESKD, amputations, albuminuria

Lack of access to care can lead to poor outcomes for patients with peripheral artery disease (PAD). We investigated the association between residential distance from home to hospital and amputation of the lower extremity among PAD patients in the Chiba peninsula, Japan. A retrospective cohort study with an average follow-up period of 2.96 years was conducted using data from 630 PAD patients who visited two hospitals in the Chiba peninsula, Japan, between 1 April 2010 to 31 March 2020. Information on disease status, residential address, and covariates was obtained from medical records. The association between amputation of a lower extremity, including toe amputation, and residential distance was evaluated by Cox proportional hazards model. Age, gender, Fontaine class, endovascular treatment, dialysis, diabetes mellitus, hypertension, dyslipidemia, current or past smoking, and aspirin use were adjusted. The median residential distance was 18.9 km (interquartile range, IQR: 22.1). Ninety-two patients (14.6%) underwent amputation of the lower extremity during the follow-up period. The longer residential distance was significantly associated with a higher risk of lower extremity amputation (hazard ratio per IQR = 1.35, 95% confidence interval, 1.01–1.82) after adjusting for covariates. Poorer access to a hospital, assessed as a longer residential distance from home to a hospital, was associated with amputation of the lower extremity among PAD patients.

Thromboendarterectomy of the common femoral artery (CFA) for occlusive disease is a crucial procedure in vascular surgery. As an outcome reference for emerging endovascular procedures and new devices, we need more robust evidence of the outcome of this gold standard technique. The purpose of this study was to report 10-year results after femoral endarterectomy (FEA). A retrospective review of medical records at our institution identified eighty consecutive patients (91 limbs) who underwent FEA for CFA lesions. Indications for FEA included 50 limbs (55%) for intermittent claudication (IC) and 39 limbs (43%) with chronic limb-threatening ischemia (CLTI). Two limbs (2%) underwent FEA to prevent hemodynamic steal during extra-anatomical bypass. Adjunctive procedures included endovascular therapy in 32%. CFAs were closed with patch angioplasty in 44%. With a mean follow-up period of 39 months, the survival rates at 3 and 8 years were 85% and 77%, respectively. Limb salvage rates were 92% and 87%. Primary patencies were 98% and 84%. Freedom from target lesion revascularization was 95% at 3 years and 91% at 8 years. Our findings support the durability of FEA, with comparable long-term procedural results in CLTI patients as well as IC patients. Since the FEA is a gate maneuver for hybrid revascularization in CLTI patients, our findings support a strategy combining open and endovascular approaches. Femoral endarterectomy remains a durable solution for common femoral occlusive disease in IC and CLTI in the era of endovascular therapy.

Peripheral arterial disease, particularly critical limb ischemia, is an area with urgent need for optimized therapies because, to date, vascular interventions often have limited life spans. In spite of initial encouraging technical success after femoropopliteal percutaneous transluminal angioplasty or stenting, postprocedural restenosis remains the major problem. The challenging idea behind the drug-coated balloon (DCB) concept is the biological modification of the injury response after balloon dilatation. Antiproliferative drugs administered via DCBs or drug-eluting stents are able to suppress neointimal hyperplasia, the main cause of restenosis. This article reviews the results of DCB treatments of femoropopliteal and infrapopliteal lesions in comparison to standard angioplasty with uncoated balloons. A systematic literature search was performed in 1) medical journals (ie, MEDLINE), 2) international registers for clinical studies (ie, www.clinicaltrials.gov), and 3) abstracts of scientific sessions. Several controlled randomized trials with follow-up periods of up to 5 years demonstrated the efficacy of paclitaxel -DCB technology. However, calcified lesions seem to affect the efficacy of DCB. Combinations of preconditioning methods with DCBs showed promising results. Although the mechanical abrasion of calcium via atherectomy or laser ablation showed favorable periprocedural results, the long-term impact on restenosis and clinical outcome has to be demonstrated. Major advantages of the DCBs are the rapid delivery of drug at uniform concentrations with a single dose, their efficacy in areas wherein stents have been contraindicated until now (ie, bifurcation, ostial lesions), and in leaving no stent scaffold behind. Reinterventions are easier to perform because DCBs leave no metal behind. Various combinations of DCBs with other treatment modalities may prove to be viable options in future. The follow-up results of clinical studies will evaluate the long-term impact of DCBs.

Background: The link between arterial stiffness and mild cognitive impairment (MCI) in patients on hemodialysis (HD) has been receiving increased attention. The purpose of this study was to investigate the relationship between cognitive function and ankle brachial index (ABI) and toe brachial index (TBI) values in patients on hemodialysis. Of the 100 participants (mean age: 67.9 years; average history of hemodialysis: 7.3 years). Of these, 46.0% had MCI. The MoCA-J scores were significantly higher in the ABI ≥ 1.06 group. However, the MoCA-J scores divided into the two groups according to the TBI cutoff value were not significantly different. In a multiple regression model with the MoCA-J scores as the objective variable, the ABI was a significantly associated factor. This study indicates that a low ABI might be associated with MCI.

An increased risk of cardiovascular events was identified in patients with peripheral artery disease (PAD). Clopidogrel is one of the most widely used antiplatelet medications. However, there are heterogeneous outcomes when clopidogrel is used to prevent cardiovascular events in PAD patients. Here, we use an artificial intelligence (AI)-assisted methodology to identify genetic factors potentially involved in the clopidogrel-resistant mechanism, which is currently unclear. Several discoveries can be pinpointed. Firstly, a high proportion (>50%) of clopidogrel resistance was found among diabetic PAD patients in Taiwan. Interestingly, our result suggests that platelet function test-guided antiplatelet therapy appears to reduce the post-interventional occurrence of major adverse cerebrovascular and cardiac events in diabetic PAD patients. Secondly, AI-assisted genome-wide association study of a single-nucleotide polymorphism (SNP) database identified a SNP signature composed of 20 SNPs, which are mapped into 9 protein-coding genes (SLC37A2, IQSEC1, WASHC3, PSD3, BTBD7, GLIS3, PRDM11, LRBA1, and CNR1). Finally, analysis of the protein connectivity map revealed that LRBA, GLIS3, BTBD7, IQSEC1, and PSD3 appear to form a protein interaction network. Intriguingly, the genetic factors seem to pinpoint a pathway related to endocytosis and recycling of P2Y12 receptor, which is the drug target of clopidogrel. Our findings reveal that a combination of AI-assisted discovery of SNP signatures and clinical parameters has the potential to develop an ethnic-specific precision medicine for antiplatelet therapy in diabetic PAD patients.

Objective: Peripheral artery disease (PAD) is a condition caused by the narrowing of limb arteries due to atherosclerosis. In recent years, polymorphisms in a number of genes have been shown to contribute to the risk of PAD development. However, whether the contribution of these inheritable factors is independent of traditional cardiovascular risk factors remains unclear. This study was an investigation of the effects of diabetes mellitus (DM) and genetic background, examined singly and together, on the pathogenesis of PAD. Methods: The effects of the factor V Leiden (G1691A), factor V H1299R, prothrombin G20210A, factor XIII V34L, B-fibrinogen -455 G>A, PAI-1 4G/5G, HPA1, MTHFR C677T, MTHFR A1298C, ACE I/D, APO B R3500Q, and APOE polymorphisms were evaluated using a cardiovascular disease strip assay (CVD StripAssay). Two groups were created: 100 patients with PAD (50 with DM, 50 without DM) and 60 controls without PAD (30 with DM, 30 without DM). Results: There was a significantly greater presence of the MTHFR A1298C and PAI 4G/5G homozygous polymorphisms in the PAD patients compared with the control group (p=0.035, p=0.004, respectively). There were no significant associations between the other genotypes and polymorphism frequencies. In the presence of DM, the PAI-1 4G/5G homozygous polymorphism was linked to the formation of PAD (p=0.021). Regression analysis indicated that the PAI-1 4G/5G gene homozygous polymorphism demonstrated a 17.1 times greater risk for DM with PAD [95% confidence interval (CI): 2.113-138.660; p=0.008] and the MTHFR A1298C homozygous polymorphism demonstrated a 316.6 times greater risk (95% CI: 10.763-9315.342; p<0.001) for the possibility of DM with PAD. Conclusion: The MTHFR A1298C and PAI 4G/5G homozygous polymorphisms may be associated with the development of PAD. The presence of the PAI 4G/5G homozygous polymorphism with DM was a powerful predictor for the development of PAD.

We investigated if corilagin can ameliorate or reverse atherosclerotic development via the toll-like receptor 4 (TLR4) signaling pathway and . Ana-1 cells or mouse peritoneal macrophages (MPMs) were stimulated with oxidized low-density lipoprotein followed by corilagin treatment. TLR4 expression in Ana-1 cells was upregulated by lentiviral transduction and downregulated by small interfering RNA. Peripheral blood mononuclear cells (PBMCs), plasma samples, and femoral arteries were collected from rats exhibiting peripheral artery disease (PAD). mRNA and protein expression of TLR4 and downstream molecules were decreased significantly by corilagin treatment in Ana-1 cells, MPMs, and rat PBMCs, and the reduction remained irrespective of downregulation or upregulation of TLR4 expression in Ana-1 cells. Corilagin also exerted a prominent effect on changes in plasma levels of cytokines and the pathologic manifestation of atherosclerosis in femoral arteries. Corilagin could ameliorate the development of atherosclerotic plaques by inhibiting the TLR4 signaling pathway in monocyte/macrophages and reduce the release of proinflammatory cytokines. This study provides a new therapeutic target and new targeting drug to oppose atherosclerosis and reveals the enormous potential of corilagin for control of PAD in humans.