The impact of diabetes mellitus on foot perfusion measured by ICG NIR fluorescence imaging.

INTRODUCTION: Diabetes Mellitus (DM) is a common chronic disease, affecting 435 million people globally. Impaired vasculature in DM patients leads to complications like lower extremity arterial disease (LEAD) and foot ulcers, often resulting in amputations. DM causes additional peripheral neuropathy leading to multifactorial wound problems. Current diagnostics often deem unreliable, but Near-Infrared Fluorescence with Indocyanine Green (ICG NIR) can be used to assess the foot perfusion. Therefore, this study explores DM's impact on foot perfusion using ICG NIR. METHODS: Baseline ICG NIR fluorescence imaging was performed in LEAD patients with and without DM. Ten perfusion parameters were extracted and analyzed to assess differences in perfusion patterns. RESULTS: Among 109 patients (122 limbs) of the included patients, 32.8% had DM. Six of ten perfusion parameters, mainly inflow-related, differed significantly between DM and non-DM patients (p-values 0.007-0.039). Fontaine stage 4 DM patients had the highest in- and outflow values, with seven parameters significantly higher (p-values 0.004-0.035). CONCLUSION: DM is associated with increased in- and outflow parameters. Patients with- and without DM should not be compared directly due to different vascular pathophysiology and multifactorial wound problems in DM patients. Quantified ICG NIR fluorescence imaging offers additional insight into the effect of DM on foot perfusion.

Efficacy of comprehensive structured exercise program on claudication pain and quality of life in type 2 diabetes mellitus with peripheral arterial disease.

Background: Peripheral arterial disease is one of the leading complications of type 2 diabetes mellitus. The primary symptom of peripheral arterial disease is claudication pain. Exercise is known to improve the claudication pain, thereby improving the quality of life. Methods: A total of 74 participants were recruited in each group and a detailed demographic assessment was done for all the participants. The study group received a comprehensive structured exercise program and standard care whereas the control group received only the standard care. Progression of the exercise was made at the 6th week of the protocol. All the outcome measures were reassessed after the 12th weeks for both study and control group. Results: The mean age of participants was 60.78 ± 11.29 (years) and 59.98 ± 11.42 (years) for the study and control group, respectively. There was a statistically significant difference in toe brachial index (p < 0.001), ankle brachial index (p < 0.001), 6-minute walk distance (p < 0.001), WHO-BREF quality of life questionnaire (p < 0.001), and walking ability ((p < 0.001) in the study group in comparison to the control group. Conclusion: In the present study we found that comprehensive structured exercise program improves the arterial indices, quality of life, walking ability and reduces claudication pain in type 2 diabetes mellitus with peripheral arterial disease. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01426-2.

Lower extremity arterial disease vs. coronary artery disease: mortality differences after revascularization.

BACKGROUND AND AIMS: Patients undergoing revascularization for lower extremity arterial disease (LEAD) may face a higher risk of mortality than those with coronary artery disease (CAD). This study aimed to characterize the difference in mortality risk between patients undergoing revascularization for LEAD and CAD and identify associated factors. METHODS: The 1-year database of 10 754 patients undergoing revascularization for CAD (n = 6349) and LEAD (n = 4405) was analysed. Poisson regression models were used to characterize interpopulation differences in mortality, adjusting for baseline clinical features, including age, sex, polyvascular disease, comorbidities, medications, and vulnerabilities. RESULTS: Individuals with LEAD were older, were more likely to have polyvascular disease, had more comorbidities, and received fewer cardioprotective drugs than those with CAD. Vulnerabilities remained more common in the LEAD group even after adjusting for these clinical features. The crude risk ratio of mortality incidence for LEAD vs. CAD was 2.91 (95% confidence interval, 2.54-3.34), attenuated to 2.14 (1.83-2.50) after controlling for age, sex, and polyvascular disease. The percentage attenuation in the excessive mortality associated with LEAD was 29%. The stepwise addition of comorbidities, medications, and vulnerabilities as adjusting factors attenuated the incidence risk ratio to 1.48 (1.26-1.72), 1.33 (1.12-1.58), and 1.17 (0.98-1.39), respectively, and increased the percentage attenuation to 64%, 73%, and 86%, respectively. CONCLUSIONS: Mortality risk was almost three-fold higher in patients undergoing revascularization for LEAD than in those with CAD. The excessive mortality was considerably attributable to inter-group differences in baseline characteristics, including potentially clinically or socially modifiable factors.

2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease" provides recommendations to guide clinicians in the treatment of patients with lower extremity peripheral artery disease across its multiple clinical presentation subsets (ie, asymptomatic, chronic symptomatic, chronic limb-threatening ischemia, and acute limb ischemia). METHODS: A comprehensive literature search was conducted from October 2020 to June 2022, encompassing studies, reviews, and other evidence conducted on human subjects that was published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through May 2023 during the peer review process, were also considered by the writing committee and added to the evidence tables where appropriate. STRUCTURE: Recommendations from the "2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with peripheral artery disease have been developed.

2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease" provides recommendations to guide clinicians in the treatment of patients with lower extremity peripheral artery disease across its multiple clinical presentation subsets (ie, asymptomatic, chronic symptomatic, chronic limb-threatening ischemia, and acute limb ischemia). METHODS: A comprehensive literature search was conducted from October 2020 to June 2022, encompassing studies, reviews, and other evidence conducted on human subjects that was published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through May 2023 during the peer review process, were also considered by the writing committee and added to the evidence tables where appropriate. STRUCTURE: Recommendations from the "2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with peripheral artery disease have been developed.

Long-Term Outcomes of a Japanese Prospective Multicenter Registry Using a Heparin-Bonded Expanded Polytetrafluoroethylene Graft for Above-the-Knee Femoropopliteal Bypasses.

BACKGROUND: Despite the widespread use of PROPATEN®, a bioactive heparin-bonded expanded polytetrafluoroethylene graft, in bypass surgery, there are only a few reports of long-term results. We evaluated the long-term results of PROPATEN®use for above-knee femoropopliteal bypass (AKFPB).Methods and Results: After PROPATEN®-based AKFPB, patients were prospectively registered at 20 Japanese institutions between July 2014 and October 2017 to evaluate long-term results. During the median follow-up of 76 months (interquartile range 36-88 months) for 120 limbs (in 113 patients; mean [±SD] age 72.7±8.1 years; 66.7% male; ankle-brachial index [ABI] 0.45±0.27; lesion length 26.2±5.7 cm; chronic limb-threatening ischemia in 45 limbs), there were 8 major amputations; however, clinical improvement was sustained (mean [±SD] ABI 0.87±0.23) and the Rutherford classification grade improved in 105 (87.5%) limbs at the latest follow-up. At 8 years, the primary patency, freedom from target-lesion revascularization, secondary patency, survival, and amputation-free survival, as estimated by the Kaplan-Meier method, were 66.3±4.8%, 71.5±4.4%, 86.5±3.4%, 53.1±5.0%, and 47.4±5.3%, respectively. CONCLUSIONS: This multicenter prospective registry-based analysis showed sustained excellent clinical improvement and secondary patency for up to 8 years following PROPATEN®-based AKFPB. PROPATEN®constitutes a durable and good revascularization option for complex superficial femoral artery lesions, especially when endovascular treatment is inappropriate or an adequate venous conduit is unavailable.

Intraluminal vs Subintimal Drug-Coated Balloon Angioplasty for the Treatment of Femoropopliteal Chronic Total Occlusions.

BACKGROUND: Whether intraluminal drug-coated balloon (DCB) angioplasty is superior to subintimal DCB angioplasty regarding femoropopliteal (FP) chronic total occlusion (CTO) outcomes has not been systematically determined. OBJECTIVES: The aim of this study was to compare the 1-year clinical outcomes of intraluminal and subintimal DCB angioplasty for the treatment of patients with symptomatic FP CTO. METHODS: This subanalysis of POPCORN (Prospective Multi-Center Registry of Drug-Coated Balloon for Femoropopliteal Disease) evaluated 469 lesions in 469 symptomatic patients with lower extremity artery disease who presented with FP CTO and underwent DCB treatment. Wire passage (intraluminal vs subintimal) was evaluated using intravascular ultrasound. The outcome measure, 1-year freedom from restenosis, was compared between subintimal and intraluminal DCB angioplasty groups after propensity score matching analysis. The Institutional Review Boards of participating centers approved this study. Informed consent was obtained from the participants or their families. RESULTS: During the median follow-up period of 14.2 months, restenosis occurred in 140 patients. After propensity score matching, the subintimal group had a significantly lower 1-year rate of freedom from restenosis than the intraluminal group (77.0% vs 84.2%, respectively; P = 0.024). Interaction analysis revealed a more marked increased risk for restenosis in the subintimal DCB angioplasty group in patients with severe calcification, low-dose DCB use, or smoking. CONCLUSIONS: The present study revealed that intraluminal DCB angioplasty was superior to subintimal DCB angioplasty for FP CTO treatment, with a significantly better 1-year rate of freedom from restenosis.

Transcriptomic Analysis of Type 2 Diabetes Mellitus Combined with Lower Extremity Atherosclerotic Occlusive Disease.

Background: The pathological damage mechanism of type 2 diabetes (T2D) and macroangiopathy is extremely complex, and T2D and arteriosclerosis obliterans have different biological behaviors and clinical features. To explore the mechanism of lower extremity arteriosclerosis occlusion (LEAOD) in T2D patients, we utilized RNA-seq to identify unique gene expression signatures of T2D and LEAOD through transcriptomic analysis. Methods: We obtained blood samples and performed RNA sequencing from four patients with T2D, five of whom had LEAOD. Another six age- and gender-matched blood samples from healthy volunteers were used for control. By exploring the general and specific differential expression analysis after transcriptome sequencing, specific gene expression patterns of T2D and LEAOD were verified. Results: Transcriptome analysis found differentially expressed genes in T2D, and T2D + LEAOD (vs normal) separately, of which 35/486 (T2D/T2D + LEAOD) were up-regulated and 1290/2970 (T2D/T2D + LEAOD) were down-regulated. A strong overlap of 571 genes across T2D, LEAOD, and coexisting conditions was mainly involved in extracellular exosomes and the transcription process. By exploring the sex difference gene expression features between T2D, T2D + LEAOD, and healthy controls, we noticed that sex chromosome-associated genes do not participate in the sexual dimorphism gene expression profiles of T2D and LEAOD. Protein-Protein Interaction Network analysis and drug target prediction provided the drug candidates to treat T2D and LEAOD. Conclusion: This study provides some evidence at the transcript level to uncover the association of T2D with LEAOD. The screened hub genes and predicted target drugs may be therapeutic targets.

Evaluation of Local Vascular Perfusion in the Lower Extremities on Intravoxel Incoherent Motion Imaging before and after Endovascular Therapy.

PURPOSE: To evaluate improvement in local vascular perfusion of the lower limbs on intravoxel incoherent motion (IVIM) imaging after endovascular therapy (EVT). MATERIALS AND METHODS: IVIM imaging was performed on 20 lower limbs of 16 patients with lower extremity arterial diseases before and after EVT. To estimate IVIM, diffusion-weighted lower-limb axial images (number of slices = 25 and slice thickness = 3.5 mm) were acquired using different b values (0, 300, and 1000 s/mm2). IVIM imaging with the simplified IVIM techniques was performed. The perfusion-related coefficient (D* [10-3 mm2/s]), perfusion fraction (f [%]), and D*f product (10-3 mm2/s %) were calculated before and 2-3 days after EVT. The ankle brachial index (ABI), mean D* (10-3 mm2/s), mean f (%), and mean D*f product (10-3 mm2/s %) before and after EVT were compared. RESULTS: Successful revascularization was achieved in all cases. After EVT, the mean ABI significantly increased from 0.59 ± 0.19 to 0.87 ± 0.15 (p < 0.001, paired t test). The mean D* (10-3 mm2/s) (22.08 ± 3.26 versus 24.87 ± 2.65, p = 0.005, paired t test), and D*f product (10-3 mm2/s%) (551.03 ± 79.02 versus 634.55 ± 76.96, p = 0.002, paired t-test) of the lower limbs significantly increased after EVT, whereas f (%) (25.00 ± 1.28 versus 25.52 ± 1.61, p = 0.261, paired t-test) did not significantly increased after EVT. CONCLUSION: D* (10-3 mm2/s) and D*f product (10-3 mm2/s %) on IVIM imaging could evaluate improvement in local vascular perfusion of the lower limbs after EVT. LEVEL OF EVIDENCE: Level 4, Case Series.

Primary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study.

BACKGROUND AND AIMS: Primary aldosteronism (PA) is an adrenal disorder of autonomous aldosterone secretion which promotes arterial injury. We aimed to explore whether PA is causally associated with lower-extremity arterial disease (LEAD). METHODS: We included 39,713 patients with diabetes and 419,312 participants without diabetes from UK Biobank. We derived a polygenic risk score (PRS) for PA based on previous genome-wide association studies (GWAS). Outcomes included LEAD and LEAD related gangrene or amputation. We conducted a two-sample Mendelian randomization analysis for PA and outcomes to explore their potential causal relationship. RESULTS: In whole population, individuals with a higher PA PRS had an increased risk of LEAD. Among patients with diabetes, compared to the subjects in the first tertile of PA PRS, subjects in the third tertile showed a 1.24-fold higher risk of LEAD (OR 1.24, 95% CI 1.03-1.49) and a 2.09-fold higher risk of gangrene (OR 2.09, 95% CI 1.27-3.44), and 1.72-fold higher risk of amputation (OR 1.72, 95% CI 1.10-2.67). Among subjects without diabetes, there was no significant association between PA PRS and LEAD, gangrene or amputation. Two-sample Mendelian randomization analysis indicated that genetically predictors of PA was significantly associated with higher risks of LEAD and gangrene (inverse variance weighted OR 1.20 [95% CI 1.08-1.34]) for LEAD, 1.48 [95% CI 1.28-1.70] for gangrene), with no evidence of significant heterogeneity or directional pleiotropy. CONCLUSIONS: Primary aldosteronism is genetically and causally associated with higher risks of LEAD and gangrene, especially among patients with diabetes. Targeting on the autonomous aldosterone secretion may prevent LEAD progression.

Current Medical Therapy and Revascularization in Peripheral Artery Disease of the Lower Limbs: Impacts on Subclinical Chronic Inflammation.

Peripheral artery disease (PAD), coronary artery disease (CAD), and cerebrovascular disease (CeVD) are characterized by atherosclerosis and inflammation as their underlying mechanisms. This paper aims to conduct a literature review on pharmacotherapy for PAD, specifically focusing on how different drug classes target pro-inflammatory pathways. The goal is to enhance the choice of therapeutic plans by considering their impact on the chronic subclinical inflammation that is associated with PAD development and progression. We conducted a comprehensive review of currently published original articles, narratives, systematic reviews, and meta-analyses. The aim was to explore the relationship between PAD and inflammation and evaluate the influence of current pharmacological and nonpharmacological interventions on the underlying chronic subclinical inflammation. Our findings indicate that the existing treatments have added anti-inflammatory properties that can potentially delay or prevent PAD progression and improve outcomes, independent of their effects on traditional risk factors. Although inflammation-targeted therapy in PAD shows promising potential, its benefits have not been definitively proven yet. However, it is crucial not to overlook the pleiotropic properties of the currently available treatments, as they may provide valuable insights for therapeutic strategies. Further studies focusing on the anti-inflammatory and immunomodulatory effects of these treatments could enhance our understanding of the mechanisms contributing to the residual risk in PAD and pave the way for the development of novel therapies.

Artificial intelligence-based predictive models in vascular diseases.

Cardiovascular disease represents a source of major health problems worldwide, and although medical and technical advances have been achieved, they are still associated with high morbidity and mortality rates. Personalized medicine would benefit from novel tools to better predict individual prognosis and outcomes after intervention. Artificial intelligence (AI) has brought new insights to cardiovascular medicine, especially with the use of machine learning techniques that allow the identification of hidden patterns and complex associations in health data without any a priori assumptions. This review provides an overview on the use of artificial intelligence-based prediction models in vascular diseases, specifically focusing on aortic aneurysm, lower extremity arterial disease, and carotid stenosis. Potential benefits include the development of precision medicine in patients with vascular diseases. In addition, the main challenges that remain to be overcome to integrate artificial intelligence-based predictive models in clinical practice are discussed.

Elevated remnant cholesterol and atherosclerotic cardiovascular disease in diabetes: a population-based prospective cohort study.

AIMS/HYPOTHESIS: Elevated remnant cholesterol is observationally and causally associated with increased risk of atherosclerotic cardiovascular disease (ASCVD) in the general population. This association is not well studied in individuals with diabetes, who are often included in clinical trials of remnant cholesterol-lowering therapy. We tested the hypothesis that elevated remnant cholesterol is associated with increased risk of ASCVD in individuals with diabetes. We also explored the fraction of excess risk conferred by diabetes which can be explained by elevated remnant cholesterol. METHODS: We included 4569 white Danish individuals with diabetes (58% statin users) nested within the Copenhagen General Population Study (2003-2015). The ASCVDs peripheral artery disease, myocardial infarction and ischaemic stroke were extracted from national Danish health registries without losses to follow-up. Remnant cholesterol was calculated from a standard lipid profile. RESULTS: During up to 15 years of follow-up, 236 individuals were diagnosed with peripheral artery disease, 234 with myocardial infarction, 226 with ischaemic stroke and 498 with any ASCVD. Multivariable adjusted HR (95% CI) per doubling of remnant cholesterol was 1.6 (1.1, 2.3; p=0.01) for peripheral artery disease, 1.8 (1.2, 2.5; p=0.002) for myocardial infarction, 1.5 (1.0, 2.1; p=0.04) for ischaemic stroke, and 1.6 (1.2, 2.0; p=0.0003) for any ASCVD. Excess risk conferred by diabetes was 2.5-fold for peripheral artery disease, 1.6-fold for myocardial infarction, 1.4-fold for ischaemic stroke and 1.6-fold for any ASCVD. Excess risk explained by elevated remnant cholesterol and low-grade inflammation was 14% and 8% for peripheral artery disease, 26% and 16% for myocardial infarction, 34% and 34% for ischaemic stroke, and 24% and 18% for any ASCVD, respectively. LDL-cholesterol did not explain excess risk, as it was not higher in individuals with diabetes. We also explored the fraction of excess risk conferred by diabetes which can be explained by elevated remnant cholesterol. CONCLUSIONS/INTERPRETATION: Elevated remnant cholesterol was associated with increased risk of ASCVD in individuals with diabetes. Remnant cholesterol and low-grade inflammation explained substantial excess risk of ASCVD conferred by diabetes. Whether remnant cholesterol should be used as a treatment target remains to be determined in randomised controlled trials.

Utility and safety of a novel method using a Wingman catheter for patients with lower extremity arterial disease complicated with severely calcified lesions: Wingman's bevel tip inner catheter removal technique-A prospective cohort study.

Background and Aims: In cases of lower extremity artery disease (LEAD) accompanied by heavily calcified lesions, endovascular treatment becomes necessary at times. To effectively address these challenging calcified lesions, we developed an innovative approach named WINNER (Wingman's bevel tip inner catheter removal) technique. This study investigated the effectiveness and safety of a novel method using the WINNER technique. Methods: This was a two-center, prospective observational study. We analyzed the clinical data of patients with LEAD complicated with severely calcified lesions who underwent the WINNER technique between January 2021 and December 2022. We investigated the patients' characteristics, target lesions, and intervention results in terms of crossing device rates and periprocedural complications. Results: A total of 35 patients were treated using the WINNER technique for LEAD complicated by severely calcified lesions. Key patient characteristics were a mean age of 75 ± 9 years, 83% male, 71% hemodialysis, 60% chronic limb-threatening ischemia, and mean lesion length of 147 ± 88 mm. Using the WINNER technique, a device crossing was achieved in 34 patients (97.1%). Wire perforation occurred in one patient, and WINNER catheter rupture occurred in three patients. Conclusions: The WINNER technique is useful for treating severely calcified lesions, and we should consider using this technique to cross devices for lesions with severe calcifications.

Clinical Characteristics of the Patient With Unmeasurable Ankle-Brachial Index in Endovascular Treatment.

Introduction Ankle-brachial index (ABI) is an important indicator to diagnose lower extremity arterial disease (LEAD). However, patients with unmeasurable ABI are sometimes excluded from the analysis and their clinical characteristics are poorly understood. Methods One hundred twenty-two consecutive Japanese subjects (mean age, 72 years), who underwent successful endovascular treatment (EVT) for lower extremity arteries at our hospital were retrospectively studied. Results Of the 122 patients, 23 (19%) patients presented an unmeasurable ABI before EVT. Five of 23 (22%) had still an unmeasurable ABI one day after EVT. Comorbidities including hypertension, diabetes, dyslipidemia, hemodialysis, smoking, ischemic heart disease, atrial fibrillation, and past-EVT history were not different between ABI measurable and unmeasurable patients. However, patients with unmeasurable ABI presented a significantly higher degree of Rutherford category and a smaller number of tibial vessel runoff than patients with measurable ABI before EVT (p<0.05 and p<0.01, respectively). There was no difference in the lesion site between the two groups. The event rate including all-cause mortality, re-EVT, lower limb amputation, and bypass surgery did not differ between two groups four years after EVT. ABI after four years of initial EVT did not differ between pre-EVT measurable and unmeasurable patients (0.96 vs. 0.84, p=0.48). Conclusions Patients with unmeasurable ABI before EVT were characterized by higher degree of Rutherford categorization and a small number of tibial vessel runoff, but there was no significant difference in outcomes during the follow-up period.

Focus on the Most Common Paucisymptomatic Vasculopathic Population, from Diagnosis to Secondary Prevention of Complications.

Middle-aged adults can start to be affected by some arterial diseases (ADs), such as abdominal aortic or popliteal artery aneurysms, lower extremity arterial disease, internal carotid, or renal artery or subclavian artery stenosis. These vasculopathies are often asymptomatic or paucisymptomatic before manifesting themselves with dramatic complications. Therefore, early detection of ADs is fundamental to reduce the risk of major adverse cardiovascular and limb events. Furthermore, ADs carry a high correlation with silent coronary artery disease (CAD). This study focuses on the most common ADs, in the attempt to summarize some key points which should selectively drive screening. Since the human and economic possibilities to instrumentally screen wide populations is not evident, deep knowledge of semeiotics and careful anamnesis must play a central role in our daily activity as physicians. The presence of some risk factors for atherosclerosis, or an already known history of CAD, can raise the clinical suspicion of ADs after a careful clinical history and a deep physical examination. The clinical suspicion must then be confirmed by a first-level ultrasound investigation and, if so, adequate treatments can be adopted to prevent dreadful complications.

Effects of RIPC on the Metabolomical Profile during Lower Limb Digital Subtraction Angiography: A Randomized Controlled Trial.

Remote ischemic preconditioning (RIPC) has demonstrated protective effects in patients with lower extremity arterial disease (LEAD) undergoing digital subtraction angiography (DSA) and/or percutaneous transluminal angioplasty (PTA). This study aimed to investigate the impact of RIPC on the metabolomical profile of LEAD patients undergoing these procedures and to elucidate its potential underlying mechanisms. A total of 100 LEAD patients were enrolled and randomly assigned to either the RIPC group (n = 46) or the sham group (n = 54). Blood samples were drawn before and 24 h after intervention. Targeted metabolomics analysis was performed using the AbsoluteIDQ p180 Kit, and changes in metabolite concentrations were compared between the groups. The RIPC group demonstrated significantly different dynamics in nine metabolites compared to the sham group, which generally showed a decrease in metabolite concentrations. The impacted metabolites included glutamate, taurine, the arginine-dimethyl-amide-to-arginine ratio, lysoPC a C24:0, lysoPC a C28:0, lysoPC a C26:1, PC aa C38:1, PC ae C30:2, and PC ae C44:3. RIPC exhibited a 'stabilization' effect, maintaining metabolite levels amidst ischemia-reperfusion injuries, suggesting its role in enhancing metabolic control. This may improve outcomes for LEAD patients. However, additional studies are needed to definitively establish causal relationships among these metabolic changes.

Peptides associated with hypertensive disorders of pregnancy as possible biomarkers for severity of lower extremity arterial disease.

BACKGROUND AND AIMS: Seven circulating peptides, consisting of 18-28 amino acids, were identified as possible biomarkers of hypertensive disorders of pregnancy (HDP) in our previous study. However, it is unknown whether these peptides are relevant to cardiovascular disease. The purpose of this study was to clarify the relationships between serum levels of these peptides and leg arterial blood flow in patients with lower extremity arterial disease (LEAD). METHODS: The subjects were 165 outpatients with LEAD. Patients with advanced LEAD (stages 5 and 6 of the Rutherford classification) were not included. Leg arterial blood flow was evaluated by ankle brachial pressure index (ABI) and % decrease in ABI after leg exercise induced by a leg loader or treadmill. Concentrations of the seven peptides with m/z 2081 (P-2081), 2091 (P-2091), 2127 (P-2127), 2209 (P-2209), 2378 (P-2378), 2858 (P-2858) and 3156 (P-3156) were measured simultaneously with a mass spectrometer. RESULTS: P-2081, P-2127 and P-2209 levels showed significant positive correlations with leg arterial blood flow, while P-2091, P-2378 and P-2858 levels showed significant inverse correlations with leg arterial blood flow. There was no significant correlation between P-3156 levels and leg arterial blood flow. The above positive and inverse associations between peptide levels and leg arterial blood flow were also found in logistic regression analysis using tertile groups divided by the concentrations of each peptide. CONCLUSIONS: Serum levels of six HDP-related peptides (P-2081, P-2091, P-2127, P-2209, P-2378 and P-2858) were associated with lower extremity arterial blood flow in patients with LEAD, and thus these peptides are possible biomarkers for severity of LEAD.

Near-Infrared Fluorescence Imaging With Indocyanine Green to Predict Clinical Outcome After Revascularization in Lower Extremity Arterial Disease.

Contemporary quality control methods are often insufficient in predicting clinical outcomes after revascularization in lower extremity arterial disease (LEAD) patients. This study evaluates the potential of near-infrared fluorescence imaging with indocyanine green to predict the clinical outcome following revascularization. Near-infrared fluorescence imaging was performed before and within 5 days following the revascularization procedure. Clinical improvement was defined as substantial improvement of pain free walking distance, reduction of rest- and/or nocturnal pain, or tendency toward wound healing. Time-intensity curves and 8 perfusion parameters were extracted from the dorsum of the treated foot. The quantified postinterventional perfusion improvement was compared within the clinical outcome groups. Successful near-infrared fluorescence imaging was performed in 72 patients (76 limbs, 52.6% claudication, 47.4% chronic limb-threatening ischemia) including 40 endovascular- and 36 surgical/hybrid revascularizations. Clinical improvement was observed in 61 patients. All perfusion parameters showed a significant postinterventional difference in the clinical improvement group (P-values <.001), while no significant differences were seen in the group without clinical improvement (P-values .168-.929). Four parameters demonstrated significant differences in percentage improvement comparing the outcome groups (P-values within .002-.006). Near-infrared fluorescence imaging has promising additional value besides clinical parameters for predicting the clinical outcome of revascularized LEAD patients.