Racial and Socioeconomic Health Disparities in Peripheral Artery Disease.

Peripheral artery disease (PAD) is a progressive atherosclerotic disease that causes lower extremity arterial stenosis or occlusion. Patients with PAD are at increased risk of myocardial infarction, stroke, limitations in ambulation, and amputation. Despite the advances in medicine and technology, the outcomes from PAD, including critical limb-threatening ischemia, acute limb ischemia amputation, and mortality, remain increased among specific racial and ethnic groups that have been historically marginalized in America, including Black, Hispanic, and American Indian individuals in the United States when compared with White persons. The purpose of this review is to summarize PAD literature that incorporates racial and ethnic disparities in PAD. There are a rising number of studies focused on the interface of racial and ethnic disparities and PAD. The majority of these studies are specifically focused on Black race, whereas there are limited studies focused on other minoritized racial and ethnic groups in the United States. The application of race and ethnicity has also been shown to play a synergistic role with socioeconomic status on PAD outcomes. Effective strategies focused on implementing policies that support quality measures and focus on social determinants of health have been shown to promote health equity and reduce disparities. Current evidence suggests that biological differences are less likely to be the leading cause of disparities in PAD between racial and ethnic groups compared with White Americans and supports a renewed focus on social determinants of health to achieve health equity.

Identification of CD141+vasculogenic precursor cells from human bone marrow and their endothelial engagement in the arteriogenesis by co-transplantation with mesenchymal stem cells.

BACKGROUND: Critical limb ischemia (CLI) is a condition characterized by insufficient blood flow to the lower limbs, resulting in severe ischemia and potentially leading to amputation. This study aims to identify novel vasculogenic precursor cells (VPCs) in human bone marrow and evaluate their efficacy in combination with bone marrow-derived mesenchymal stem cells (BM-MSCs) for the treatment of CLI. METHODS: Ex vivo cultured VPCs and BM-MSCs from bone marrow were characterized and their effects on neovascularization and long-term tissue regeneration were tested in a mouse CLI model. RESULTS: VPCs, expressing high levels of hepatocyte growth factor and c-MET, were identified from human bone marrow aspirates. These cells exhibited strong vasculogenic capacity in vitro but possessed a cellular phenotype distinct from those of previously reported endothelial precursor cells in circulation or cord blood. They also expressed most surface markers of BM-MSCs and demonstrated multipotent differentiation ability. Screening of 376 surface markers revealed that VPCs uniquely display CD141 (thrombomodulin). CD141+VPCs are present in BM aspirates as a rare population and can be expanded ex vivo with a population doubling time of approximately 20 h, generating an elaborate vascular network even under angiogenic factor-deficient conditions and recruiting BM-MSCs to the network as pericyte-like cells. Intramuscular transplantation of a combination of human CD141+VPCs and BM-MSCs at a ratio of 2:1 resulted in limb salvage, blood flow recovery, and regeneration of large vessels in the femoral artery-removed CLI model, with an efficacy superior to that of singular transplantation. Importantly, large arteries and arterioles in dual cell transplantation expressed human CD31 in the intima and human α-smooth muscle actin in media layer at 4 and 12 weeks, likely indicating their lineage commitment to endothelial cells and vascular smooth muscle, respectively, in vivo. CONCLUSION: Dual-cell therapy using BM-derived CD141+ VPCs and BM-MSCs holds potential for further development in clinical trials to treat peripheral artery disease and diabetic ulcers.

Neutrophil-to-lymphocyte ratio as a prognostic biomarker in patients with peripheral artery disease: A systematic review and meta-analysis.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is a simple and routinely obtained parameter reflecting systemic inflammation, including in peripheral artery disease (PAD). METHODS: This systematic review aimed to assess the role of NLR as a prognostic biomarker in patients with PAD. A systematic search was conducted across PubMed, ScienceDirect, Web of Science, Scopus, ProQuest, EBSCO, and Cochrane. Random-effects meta-analysis was used to pool risk ratios, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). A bivariate model was used to generate summary receiver operating characteristics with the corresponding area under the curve (AUC). RESULTS: This review included 5243 patients with PAD from nine eligible studies. High NLR corresponded to at least a twofold increased risk of all-cause mortality (ACM), major adverse limb events (MALE), and major adverse cardiovascular events (MACE). NLR's performance was good for predicting 1-year ACM (AUC 0.71 [95% CI: 0.59-0.79], sensitivity 58.2% [95% CI: 45.3-71.0], specificity 72.6% [95% CI: 65.6-79.62], PPV 41.0% [95% CI: 31.2-50.7], NPV 82.7% [95% CI: 74.1-91.3]) and 1-year MALE (AUC 0.78 [95% CI: 0.75-0.80], sensitivity 65.4% [95% CI: 41.6-89.2], specificity 77.7% [95% CI: 71.0-84.3], PPV 53.7% [95% CI: 47.3-60.1], NPV 83.91% [95% CI: 73.2-94.6]). However, these values tended to decrease as the follow-up duration extended, except for the pooled specificities, which exhibited the opposite pattern. CONCLUSION: NLR emerges as a simple and cost-effective prognostic biomarker with decent performance for poor outcomes in patients with PAD (PROSPERO Registration No.: CRD42023486607).

Quantifying patients' preferences on tradeoffs between mortality risk and reduced need for target vessel revascularization for claudication.

BACKGROUND: In 2019, the US Food and Drug Administration issued a warning that symptomatic relief from claudication using paclitaxel-coated devices might be associated with an increase in mortality over 5 years. We designed a discrete-choice experiment (DCE) to quantify tradeoffs that patients would accept between a decreased risk of clinically driven target-vessel revascularization (CDTVR) and increased mortality risk. METHODS: Patients with claudication symptoms were recruited from seven medical centers to complete a web-based survey including eight DCE questions that presented pairs of hypothetical device profiles defined by varying risks of CDTVR and overall mortality at 2 and 5 years. Random-parameters logit models were used to estimate relative preference weights, from which the maximum-acceptable increase in 5-year mortality risk was derived. RESULTS: A total of 272 patients completed the survey. On average, patients would accept a device offering reductions in CDTVR risks from 30% to 10% at 2 years and from 40% to 30% at 5 years if the 5-year mortality risk was less than 12.6% (95% CI: 11.8-13.4%), representing a cut-point of 4.6 percentage points above a baseline risk of 8%. However, approximately 40% chose the device alternative with the lower 5-year mortality risk in seven (20.6%) or eight (18.0%) of the eight DCE questions regardless of the benefit offered. CONCLUSIONS: Most patients in the study would accept some incremental increase in 5-year mortality risk to reduce the 2-year and 5-year risks of CDTVR by 20 and 10 percentage points, respectively. However, significant patient-level variability in risk tolerance underscores the need for systematic approaches to support benefit-risk decision making.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Dynamic perioperative platelet activity and cardiovascular events in peripheral artery disease.

OBJECTIVE: Patients with peripheral artery disease (PAD) undergo lower extremity revascularization (LER) for symptomatic relief or limb salvage. Despite LER, patients remain at increased risk of platelet-mediated complications, such as major adverse cardiac and limb events (MACLEs). Platelet activity is associated with cardiovascular events, yet little is known about the dynamic nature of platelet activity over time. We, therefore, investigated the change in platelet activity over time and its association with long-term cardiovascular risk. METHODS: Patients with PAD undergoing LER were enrolled into the multicenter, prospective Platelet Activity and Cardiovascular Events study. Platelet aggregation was assessed by light transmission aggregometry to submaximal epinephrine (0.4 µmol/L) immediately before LER, and on postoperative day 1 or 2 (POD1 or POD2) and 30 (POD30). A hyperreactive platelet phenotype was defined as >60% aggregation. Patients were followed longitudinally for MACLEs, defined as the composite of death, myocardial infarction, stroke, major lower extremity amputation, or acute limb ischemia leading to reintervention. RESULTS: Among 287 patients undergoing LER, the mean age was 70 ± 11 years, 33% were female, 61% were White, and 89% were on baseline antiplatelet therapy. Platelet aggregation to submaximal epinephrine induced a bimodal response; 15.5%, 16.8%, and 16.4% of patients demonstrated a hyperreactive platelet phenotype at baseline, POD1, and POD30, respectively. Platelet aggregation increased by 18.5% (P = .001) from baseline to POD1, which subsequently returned to baseline at POD30. After a median follow-up of 19 months, MACLEs occurred in 165 patients (57%). After adjustment for demographics, clinical risk factors, procedure type, and antiplatelet therapy, platelet hyperreactivity at POD1 was associated with a significant hazard of long-term MACLE (adjusted hazard ratio, 4.61; 95% confidence interval, 2.08-10.20; P < .001). CONCLUSIONS: Among patients with severe PAD, platelet activity increases after LER. Platelet hyperreactivity to submaximal epinephrine on POD1 is associated with long-term MACLE. Platelet activity after LER may represent a modifiable biomarker associated with excess cardiovascular risk.

Association of health status and hospitalization risk for peripheral artery disease in the PORTRAIT registry.

BACKGROUND: Healthcare utilization for patients with peripheral artery disease (PAD) is high, but stratifying patients' risk of hospitalization at initial evaluation is challenging. We examined the association between health status at PAD presentation and risk of (1) combined all-cause hospital admissions and emergency department (ED) visits and (2) all-cause hospital admissions. METHODS: Patients with claudication enrolled at US sites in the PORTRAIT registry were included. Health status was assessed using the Peripheral Artery Questionnaire (PAQ), a PAD-specific patient-reported outcome measure. Crude overall and cause-specific hospital admissions and ED visits were reported by PAQ overall summary score (PAQ-OS) ranges (0-24, 25-49, 50-74, and 75-100). Kaplan-Meier survival and unadjusted and adjusted Cox proportional hazards models examined the association between baseline PAQ scores and (1) combined all-cause hospital admissions or ED visits and (2) all-cause hospital admissions over 12 months. RESULTS: Of 796 patients, 349 (44%) had a hospital admission or ED visit over 12 months. Patients in the lowest (PAQ-OS = 0-24) versus the highest range (PAQ-OS = 75-100) had higher rates of 12-month (53.3% vs 22.4%) hospital admission and ED visits. In the adjusted model, each 10-point decrease in PAQ-OS was associated with a higher risk of all-cause hospital admission and ED visits (HR = 1.1, 95% CI 1.1-1.2, p < 0.0010) and all-cause hospital admission (HR = 1.1, 95% CI 1.1-1.2, p < 0.0010) at 12 months. CONCLUSION: PAD-specific health status is associated with an increased risk of healthcare utilization. Baseline health status may help stratify risk in patients with PAD, although replication and further validation of results are necessary.

Trends in patient characteristics and mortality among Medicare patients diagnosed with peripheral artery disease.

INTRODUCTION: Peripheral artery disease (PAD) is a well-described risk factor for mortality, but few studies have examined secular trends in mortality over time for patients with PAD. We characterized trends in mortality in patients with PAD in recent years among Medicare patients. METHODS: We used Medicare claims to identify patients with a new diagnosis code for PAD between January 1, 2006 and December 31, 2018 using International Classification of Diseases (ICD) diagnosis codes. The primary outcome of interest was the 1-year all-cause age-adjusted mortality rate. Our secondary outcome was the 5-year all-cause mortality rate. Multivariable regression was used to identify factors which predict mortality at 1 year. RESULTS: We identified 4,373,644 patients with a new diagnosis code for PAD during the study period. Between 2006 and 2018, 1-year all-cause age-adjusted mortality declined from 12.6% to 9.9% (p < 0.001). One-year crude all-cause mortality also declined from 14.6% to 9.5% (p < 0.001). Similar results were observed for 5-year age-adjusted mortality rates (40.9% to 35.2%, p < 0.001). Factors associated with increased risk of death at 1 year included age ⩾ 85 years (hazard ratio [HR] 3.030; 95% CI 3.008-3.053) and congestive heart failure (HR 1.86; 95% CI 1.85-1.88). Patients who were regularly dispensed statins, ace-inhibitors, beta-blockers, antithrombotic agents, and anticoagulants all had lower mortality (range OR 0.36; CI 0.35-0.37 for statins to OR 0.60; CI 0.59-0.61 for anticoagulants; all p < 0.001). CONCLUSION: Among US Medicare patients diagnosed with PAD between 2006 and 2019, 1-year age-adjusted mortality declined by 2.7%. This decline in mortality among PAD patients occurred in the context of a younger mean age of diagnosis of PAD and improved cardiovascular prevention therapy.

The ankle-brachial index, gastrocnemius mitochondrial respirometry, and walking performance in people with and without peripheral artery disease.

Background: Mitochondrial abnormalities exist in lower-extremity peripheral artery disease (PAD), yet the association of the ankle-brachial index (ABI) with mitochondrial respiration in gastrocnemius muscle is unknown. The association of gastrocnemius mitochondrial respiration with 6-minute walk distance in PAD is unknown. Objective: To describe associations of the ABI with mitochondrial respiratory function in gastrocnemius muscle biopsies and associations of gastrocnemius mitochondrial respirometry with 6-minute walk distance in people with and without PAD. Methods: People with (ABI ⩽ 0.90) and without (ABI 1.00-1.40) PAD were enrolled. ABI and 6-minute walk distance were measured. Mitochondrial function of permeabilized myofibers from gastrocnemius biopsies was measured with high-resolution respirometry. Results: A total of 30 people with PAD (71.7 years, mean ABI: 0.64) and 68 without PAD (71.8 years, ABI: 1.17) participated. In non-PAD participants, higher ABI values were associated significantly with better mitochondrial respiration (Pearson correlation for maximal oxidative phosphorylation PCI+II: +0.29, p = 0.016). In PAD, the ABI correlated negatively and not significantly with mitochondrial respiration (Pearson correlation for PCI+II: -0.17, p = 0.38). In people without PAD, better mitochondrial respiration was associated with better 6-minute walk distance (Pearson correlation: +0.51, p < 0.001), but this association was not present in PAD (Pearson correlation: +0.10, p = 0.59). Conclusions: Major differences exist between people with and without PAD in the association of gastrocnemius mitochondrial respiration with ABI and 6-minute walk distance. Among people without PAD, ABI and walking performance were positively associated with mitochondrial respiratory function. These associations were not observed in PAD.

Competing risk analysis to estimate amputation incidence and risk in lower-extremity peripheral artery disease.

Background: Patients with peripheral artery disease face high amputation and mortality risk. When assessing vascular outcomes, consideration of mortality as a competing risk is not routine. We hypothesize standard time-to-event methods will overestimate major amputation risk in chronic limb-threatening ischemia (CLTI) and non-CLTI. Methods: Patients undergoing peripheral vascular intervention from 2017 to 2018 were abstracted from the Vascular Quality Initiative registry and stratified by mean age (⩾ 75 vs < 75 years). Mortality and amputation data were obtained from Medicare claims. The 2-year cumulative incidence function (CIF) and risk of major amputation from standard time-to-event analysis (1 - Kaplan-Meier and Cox regression) were compared with competing risk analysis (Aalen-Johansen and Fine-Gray model) in CLTI and non-CLTI. Results: A total of 7273 patients with CLTI and 5095 with non-CLTI were included. At 2-year follow up, 13.1% of patients underwent major amputation and 33.4% died without major amputation in the CLTI cohort; 1.3% and 10.7%, respectively, in the non-CLTI cohort. In CLTI, standard time-to-event analysis overestimated the 2-year CIF of major amputation by 20.5% and 13.7%, respectively, in patients ⩾ 75 and < 75 years old compared with competing risk analysis. The standard Cox regression overestimated adjusted 2-year major amputation risk in patients ⩾ 75 versus < 75 years old by 7.0%. In non-CLTI, the CIF was overestimated by 7.1% in patients ⩾ 75 years, and the adjusted risk was overestimated by 5.1% compared with competing risk analysis. Conclusions: Standard time-to-event analysis overestimates the incidence and risk of major amputation, especially in CLTI. Competing risk analyses are alternative approaches to estimate accurately amputation risk in vascular outcomes research.

Ultrasound enhancing agents in cardiovascular imaging: expanding horizons beyond coronary arteries.

From its inception as a two-dimensional snapshot of the beating heart, echocardiography has become an indelible part of cardiovascular diagnostics. The integration of ultrasound enhancing agents (UEAs) marks a pivotal transition, enhancing its diagnostic acumen beyond myocardial perfusion. These agents have refined echocardiography's capacity to visualize complex cardiac anatomy and pathology with unprecedented clarity, especially in non-coronary artery disease contexts. UEAs aid in detailed assessments of myocardial viability, endocardial border delineation in left ventricular opacification, and identification of intracardiac masses. Recent innovations in UEAs, accompanied by advancements in echocardiographic technology, offer clinicians a more nuanced view of cardiac function and blood flow dynamics. This review explores recent developments in these applications and future contemplated studies.

Benefits and Challenges of Drug-Coated Balloons in Peripheral Artery Disease: From Molecular Mechanisms to Clinical Practice.

Multiple clinical trials have reported favorable outcomes after drug-coated balloon therapy for peripheral artery disease in above-the-knee and below-the-knee lesions and in both de novo and in-stent restenosis. However, there are still insufficient data to identify and tackle the risk factors associated with a higher risk of restenosis, which is the primary concern for patients who are treated with an endovascular approach. A modern armamentarium, which includes improved lesion preparation techniques such as plaque modification balloons, mechanical atherectomy, intravascular lithotripsy, and imaging, is crucial for obtaining better long-term clinical outcomes. Moreover, a better understanding of the molecular properties of drug-coated balloons has led to improved devices that could tackle the shortcomings of previous generations. This comprehensive review focuses on drug-coated balloon technology as a tool to treat peripheral artery disease and the effects of the molecular mechanisms involved in preventing vascular restenosis.

Influence of pseudoxanthoma elasticum on the lipid profile and prognostic implications.

Background: Pseudoxanthoma elasticum (PXE) is a rare, inherited disease characterised by specific skin lesions, progressive loss of vision and early onset atherosclerosis. Atherosclerosis in PXE leads to an increased rate of vascular occlusion and severe intermittent claudication. Although genetically determined, the individual course of PXE is highly variable. Up to now, there is no sufficient parameter to identify individuals at risk of rapid disease progression. This present study focused the lipid profile of patients with PXE and its possible influence on the clinical severity of peripheral artery disease (PAD). Patients and methods: 112 patients with PXE were retrospectively screened. Patients without a complete lipid profile consisting of total cholesterol (TC), triglycerides (TGC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and Lipoprotein(a) (Lp[a]) where excluded as well as patients with already initiated lipid-lowering therapy. 52 patients met the inclusion criteria. An age-adjusted ordinal regression model was applied to determine the association of each lipid fraction with the severity of PAD assessed as Fontaine classification. Results: The lipid profile of patients with PXE was unremarkable (TGC: 135.8±105.8 mg/dl; TC: 172.5±44.4 mg/dl; HDL: 63.0±18.2 mg/dl; Lp[a]: 64.7±93.5 nmol/l). Ordinal regression showed a significant association of Lp(a) with the severity of PAD with an odds ratio of 1.01 (1.00-1.02; p = 0.004), whereas the other fractions of the lipid profile had no significant influence. Conclusions: This study provides the largest evaluation of blood lipids up to now and the first characterization of Lp(a) levels in patients with PXE. We were able to provide first evidence of a correlation between elevated levels of Lp(a) and the severity of PAD. The present results suggest that determination of Lp(a) in early stages of PXE could help to identify patients at risk of rapid disease progression and with the need of intensified walking exercise training.

Importance of Using Angiography for the Early Detection of Chronic Limb Ischemia in Diabetic Foot Wounds.

Peripheral artery disease (PAD) affects millions of people worldwide, presenting with varying symptom severity, including chronic total occlusion of arteries, and occasionally, limb amputation. There are various interventions, such as atherectomy and the use of drug-coated balloons and stents, which have been developed to revascularize affected ischemic regions. However, each interventional approach must be individualized due to a patient's unique underlying conditions. Comorbid conditions, especially diabetes, play a significant role in PAD, as poorly controlled diabetes can accelerate PAD progression. For this reason, an early and accurate diagnosis of PAD is crucial, especially when symptoms may present dissimilar to classic PAD symptoms, often leading to misdiagnosis. The presented cases highlight the tailored interventions to revascularize arteries in patients with diabetic foot wounds utilizing catheters, stents, guidewires, and balloons, made possible after early angiogram. These interventions have been promising in treating PAD patients, and highlight the need for early diagnosis and timely and customized interventions to prevent limb amputation and mitigate potential complications.

Impact of the Coexisting Coronary Artery Disease on Five-Year Outcomes in Lower Extremity Artery Disease Patients Without Chronic Limb-Threatening Ischemia.

Coronary artery disease (CAD) is often noted in patients with lower-extremity artery disease (LEAD). However, the effects of CAD on patients with LEAD have not been clearly investigated. In this study, to investigate the effect of CAD on patients with LEAD without chronic limb-threatening ischemia (CLTI), we compared the five-year clinical outcomes of patients with and without CAD. Between 2014 and 2017, 246 patients with symptomatic LEAD without CLTI underwent endovascular treatment. Patients with a history of CAD revascularization or CAD defined by CAD studies were divided into CAD groups, and others were non-CAD groups. After excluding ineligible patients, propensity matching produced 40 patients in each group, and clinical outcomes were compared between the groups. Using five years of Kaplan-Meier analysis between the CAD and non-CAD groups, no significant differences were observed in survival (90.0% vs 92.5%, p=0.693), freedom from cardiovascular events (42.5% vs 57.5%, p=0.110), freedom from LEAD revascularization (67.5% vs 67.5%, p=0.940), and freedom from CLTI (100% vs. 95.0%, p=0.148). However, significant differences were observed in freedom from CAD revascularization (67.5% vs 97.5%, p<0.001) and freedom from symptomatic CAD (85.0% vs 97.5%, p=0.048). Our results suggest that in patients with LEAD without CLTI, CAD caused increased CAD revascularization and symptomatic CAD. However, CAD did not affect survival, cardiovascular events, LEAD revascularization, or CLTI in such patients. When CAD was observed in patients with LEAD without CLTI, more frequent follow-up of CAD may improve the long-term clinical outcomes of such patients.

Development of a Tetherless Bioimpedance Device That Uses Morphologic Changes to Predict Blood Flow Restrictions Mimicking Peripheral Artery Disease Progression.

A tetherless multi-targeted bioimpedance device was designed, modeled, built, and tested for measuring arterial pulse and, using morphological analysis, its potential for monitoring blood flow restrictions that mimic Peripheral Artery Disease (PAD) was assessed across multiple peripheral arteries. Specifically, we first developed a small form factor, tetherless, bioimpedance device, based on high-frequency structure simulator (HFSS) simulations. After designing and building the device we then tested it in vivo on human subjects on multiple arteries and found that we did not need to modify the gain on the device compared to the bench top system. Further, it was found that changes in the morphology of the bioimpedance signal over time, depicted through the ratio of the first and second harmonic in the signal frequency, could be used to predict blood flow restrictions that mimic peripheral artery disease (PAD). The HFSS simulations helped guide the modulation frequency selection and the placement of the bioimpedance electrodes. We built the device and compared it to two commercially available bioimpedance devices and it was shown to demonstrate a distinct advantage in its multi-target capability, enabling more accurate pulse measurements from different arteries without the need for tuning the circuit for each artery. Comparing the ratio of the 1st and 2nd harmonics as a function of the blood flow restriction, the two commercial devices showed a maximum error across arteries of between 22% and 27% depending on the measurement location, whereas our system consistently displayed a stable value of just below 4%. With this system, there is the potential for comprehensive and personalized medical examinations for PAD at the point of care (POC).

Benefits of Taurisolo in Diabetic Patients with Peripheral Artery Disease.

Trimethyl-N-oxide (TMAO) has been linked to peripheral artery disease (PAD). TaurisoloⓇ is a natural, balanced phytocomplex containing resveratrol, quercetin, catechins, procianidins, gallic acid, and caffeic acid. Numerous studies have shown that TaurisoloⓇ reduces the damage of TMAO and exerts a protective effect on endothelial cells (ECs). The aim of this randomized, double-blind, single-center study was to evaluate the effects of TaurisoloⓇ on claudication in patients with PAD (Rutheford grade I, category II, Fontaine Classification: Stage IIA, American Medical Association Whole Person Impairment Classification: Class 0-WPI 0%) in two parallel groups of 31 patients. The primary outcomes were an increase in the pain-free walking distance and the ankle/brachial pressure index at the beginning and at the end of the treatment with Taurisolo. The secondary endpoint was the serum TMAO changes. The claudication distance improved by 14.1% in the Taurisolo group and by 2.0% in the placebo group, while the maximal distance increased by 15.8% and 0.6% only, respectively (both p < 0.05). The TMAO plasma levels decreased from 3.97 ± 2.13 micromole/L to 0.87 ± 0.48 (p < 0.0001) in the treated group. All these changes were highly significant both in univariate mixed models as well as in the adjusted model. Ultimately, TaurisoloⓇ might be an effective intervention to ameliorate intermittent claudication.