A retrospective analysis on optimal medical therapy for patients with symptomatic lower extremity peripheral artery disease: a French observational study.

OBJECTIVE: Patients with symptomatic lower extremity artery disease (LEAD) should have an optimal management in terms of lipid goal [i.e. controlled LDL-cholesterol (LDLc)] and medical treatment (triple therapy with an antiplatelet agent, a statin and an angiotensin-converting enzyme inhibitor or a angiotensin-receptor antagonist). Prevalence of LEAD patients with a LDLc < 0.55 g/l is unknown. Aims of this study were to: (i) describe the prevalence of patients with a LDLc < 0.55 g/l, (ii) describe the prevalence of patients with an optimal medical treatment; (iii) compare this management between patients with a vascular surgery history and those without a vascular surgery history; and (iv) evaluate the number of patients eligible for new lipid-lowering therapies according to FOURIER and REDUCE-IT criteria. METHODS: In this single-center retrospective study, prevalence is expressed as numbers and percentages. Comparison of the number of well managed patients between LEAD patients with a vascular surgery history and those without was performed. Number of patients who would be eligible for FOURIER and REDUCE-IT studies were calculated. RESULTS: Among the LEAD patients included in the analysis (n = 225), only 12.4% (n = 28) had a LDLc < 0.55 g/L. The prevalence of patients who received the optimal medical treatment was 50.7% (n = 114). There was no statistical difference in the prevalence of patients with and without vascular surgery history achieving the LDLc goal (n = 9 (10.6%) vs. n = 19 (13.6%); p = not significant). Ninety-three patients (46.0%) would be eligible for EVOLOCUMAB treatment according to the Fourier study design whereas 17 patients (8.4%) would be eligible for treatment with ICOSAPENT ETHYL according to the REDUCE-IT study design. CONCLUSION: A majority of LEAD patients did not reach the LDLc goals. LEAD patients with a vascular surgery history did not experience a better management whereas they had a more consistent follow-up.

Proportion of Peripheral Arterial Disease in Patients with Chronic Kidney Disease.

Among the different complications of chronic kidney diseases, peripheral arterial disease is not uncommon. Though it is an indicator of widespread atherosclerosis, sometimes it is neglected in CKD patients. Our study was done to evaluate the frequency and pattern of PAD in chronic kidney disease patients admitted in a tertiary care hospital of Bangladesh. One hundred (100) admitted patients of CKD were taken by nonrandom purposive sampling considering inclusion and exclusion criteria. After clinical evaluation and Ankle brachial index (ABI) measurement 5 cc venous blood was collected and sent to Clinical Pathology and Biochemistry department of CMCH. Data was collected in a structured proforma and analyzed. Among the 100 patients, 2.0% patient belonged to stage 3, 28.0% were in stage 4 and remaining 70.0% were in stage 5. We found the proportion of PAD in CKD were 18.0%. Among 18 PAD patients, 66.67% were in stage 5, 22.22% in stage 4 and 11.11% in stage 3. Regarding right lower limb 12 patients had some PAD, 3 patients had moderate PAD, 2 patients had borderline and 1 patient had calcified PAD. For left lower limb, 10 patients had some PAD, 4 patients had moderate PAD, 4 patients had borderline PAD. The mean AB) of the PAD patients for right limb was 0.87 and for left limb 0.84. 50.0-55.0% patients were asymptomatic. Among the PAD patients 38.9% had DM, 72.2% had HTN, 33.3% had both DM and HTN, 44.4% had other vascular events, 55.6% were smokers, 33.3% had dyslipidemia and 22.2% had family history of PAD. Renal diseases seem to have a strong association with vascular disease and PAD is not uncommon.

Diet and exercise in relation to lower extremity artery disease.

Adherence to the Mediterranean diet (MeD) has been associated with a reduced incidence of peripheral arterial disease (PAD)/lower extremity arterial disease (LEAD) in observational trials and in a randomized trial. In secondary prevention, a lower hazard ratio for composite major adverse cardiovascular events has been associated with better adherence to MeD in a relatively small, randomized trial. This has not been confirmed in a sub-analysis of a large interventional trial of dual antithrombotic treatment. The effects of vegetarian, vegan or low carbohydrate/ketogenic diets on the incidence and outcomes of PAD/LEAD are not known. While abdominal obesity is associated with diabetes mellitus and PAD/LEAD, the lowest incidence of PAD/LEAD has been found in subjects with a body mass index 25-29.9 kg/m2. Malnutrition is a negative prognostic factor for survival of patients with chronic limb threatening ischemia. Physical activity (PA) is an acute stressor, but habitual recreational PA results in beneficial adaptations and improved health. In observational studies, lower levels of exercise and lower physical fitness have been associated with more prevalent PAD/LEAD. In contrast to coronary artery disease, that shows a reverse J-shaped relationship between long-term endurance exercise and coronary atherosclerosis, such a relationship is not known for PAD/LEAD. A general recommendation for maintaining cardiovascular health is performing regular moderate-intensity exercise with some vigorous-intensity aerobic PA, and resistance exercise at least twice a week. Combinations of healthy behaviors are more effective in preventing PAD/LEAD than a single behavioral component. In treatment of PAD/LEAD causing intermittent claudication, supervised walking training is recommended among measures of first-line treatment, while unsupervised walking training should be considered as an alternative.

Toe-brachial index and toe systolic blood pressure for the diagnosis of peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) of the lower limbs is caused by atherosclerotic occlusive disease in which narrowing of arteries reduces blood flow to the lower limbs. PAD is common; it is estimated to affect 236 million individuals worldwide. Advanced age, smoking, hypertension, diabetes and concomitant cardiovascular disease are common factors associated with increased risk of PAD. Complications of PAD can include claudication pain, rest pain, wounds, gangrene, amputation and increased cardiovascular morbidity and mortality. It is therefore clinically important to use diagnostic tests that accurately identify PAD. Accurate and timely detection of PAD allows clinicians to implement appropriate risk management strategies to prevent complications, slow progression or intervene when indicated. Toe-brachial index (TBI) and toe systolic blood pressure (TSBP) are amongst a suite of non-invasive bedside tests used to detect PAD. Both TBI and TSBP are commonly utilised by a variety of clinicians in different settings, therefore a systematic review and meta-analysis of their diagnostic accuracy is warranted and highly relevant to inform clinical practice. OBJECTIVES: To (1) estimate the accuracy of TSBP and TBI for the diagnosis of PAD in the lower extremities at different cut-off values for test positivity in populations at risk of PAD, and (2) compare the accuracy of TBI and TSBP for the diagnosis of PAD in the lower extremities. Secondary objectives were to investigate several possible sources of heterogeneity in test accuracy, including the following: patient group tested (people with type 1 or type 2 diabetes, people with renal disease and general population), type of equipment used, positivity threshold and type of reference standard. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the MEDLINE, Embase, CINAHL, Web of Science, LILACS, Zetoc and DARE databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 27 February 2024. SELECTION CRITERIA: We included diagnostic case-control, cross-sectional, prospective and retrospective studies in which all participants had either a TSBP or TBI measurement plus a validated method of vascular diagnostic imaging for PAD. We needed to be able to cross-tabulate (2 x 2 table) results of the index test and the reference standard to include a study. To be included, study populations had to be adults aged 18 years and over. We included studies of symptomatic and asymptomatic participants. Studies had to use TSBP and TBI (also called toe-brachial pressure index (TBPI)), either individually, or in addition to other non-invasive tests as index tests to diagnose PAD in individuals with suspected disease. We included data collected by photoplethysmography, laser Doppler, continuous wave Doppler, sphygmomanometers (both manual and aneroid) and manual or automated digital equipment. DATA COLLECTION AND ANALYSIS: Two review authors independently completed data extraction using a standardised form. We extracted data to populate 2 x 2 contingency tables when available (true positives, true negatives, false positives, false negatives). Where data were not available to enable statistical analysis, we contacted study authors directly. Two review authors working independently undertook quality assessment using QUADAS-2, with disagreements resolved by a third review author. We incorporated two additional questions into the quality appraisal to aid our understanding of the conduct of studies and make appropriate judgements about risk of bias and applicability. MAIN RESULTS: Eighteen studies met the inclusion criteria; 13 evaluated TBI only, one evaluated TSBP only and four evaluated both TBI and TSBP. Thirteen of the studies used colour duplex ultrasound (CDU) as a reference standard, two used computed tomography angiography (CTA), one used multi-detector row tomography (MDCT), one used angiography and one used a combination of CDU, CTA and angiography. TBI was investigated in 1927 participants and 2550 limbs. TSBP was investigated in 701 participants, of which 701 limbs had TSBP measured. Studies were generally of low methodological quality, with poor reporting of participant recruitment in regard to consecutive or random sampling, and poor reporting of blinding between index test and reference standard, as well as timing between index test and reference standard. The certainty of evidence according to GRADE for most studies was very low. AUTHORS' CONCLUSIONS: Whilst a small number of diagnostic test accuracy studies have been completed for TBI and TSBP to identify PAD, the overall methodological quality was low, with most studies providing a very low certainty of evidence. The evidence base to support the use of TBI and TSBP to identify PAD is therefore limited. Whilst both TBI and TSBP are used extensively clinically, the overall diagnostic performance of these tests remains uncertain. Future research using robust methods and clear reporting is warranted to comprehensively determine the diagnostic test accuracy of the TBI and TSBP for identification of PAD with greater certainty. However, conducting such research where some of the reference tests are invasive and only clinically indicated in populations with known PAD is challenging.

Accuracy of ankle-brachial index in screening for peripheral arterial disease in people with diabetes.

Although the ankle-brachial index (ABI) presents overall satisfactory accuracy, its sensitivity in the context of screening strategies does not ensure the detection of all individuals with peripheral arterial disease (PAD), especially in clinical situations where there is calcification of the arterial media layer. This study evaluated the accuracy of ABI in screening PAD among individuals with diabetes mellitus (DM) in a community setting. An observational study included only individuals with DM. ABI measurement was performed, and the lower limb duplex ultrasound (DU) was used as the reference standard for PAD diagnosis. Sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (LR+ and LR-) of ABI were assessed. The analysis included 194 limbs from 99 participants, with a PAD prevalence identified by DU of 15.98%. ABI demonstrated an accuracy of 87.63%, with a sensitivity of 35.48%, specificity of 97.55%, PPV of 73.33%, NPV of 89.83%, LR+ of 14.46, and LR- of 0.66. ABI showed high specificity but limited sensitivity in detecting PAD among individuals with DM in a community setting. An LR- of 0.66 suggests that a normal ABI result reduces but does not eliminate the possibility of PAD, highlighting the importance of complementary diagnostic approaches to enhance accuracy in identifying PAD in high-risk patients, such as those with DM. Incorporating additional diagnostic methods may be necessary to improve the effectiveness of PAD screening in this group.

Peripheral artery disease and risk of kidney outcomes: The Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND AND AIMS: The potential impact of peripheral artery disease (PAD) on kidney outcomes is not well understood. The aim of this study was to explore the association between PAD and end-stage kidney disease (ESKD) and chronic kidney disease (CKD). METHODS: Among 14,051 participants (mean age 54 [SD 6 years]) from the Atherosclerosis Risk in Communities study, we categorized PAD status as symptomatic PAD (intermittent claudication or leg revascularization), asymptomatic PAD (ankle-brachial index [ABI] ≤0.90 without clinical history of symptoms), and ABI 0.91-1.00, 1.01-1.10, 1.11-1.20 (reference), 1.21-1.30, and >1.30. We evaluated their associations with two kidney outcomes: ESKD (the need of renal replacement therapy or death due to kidney disease) and CKD (ESKD cases or an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 with a ≥25 % decline from the baseline) using multivariable Cox proportional hazards models. RESULTS: Over ∼30 years of follow-up, there were 598 cases of incident ESKD and 4686 cases of incident CKD. After adjusting for potential confounders, both symptomatic PAD and asymptomatic PAD conferred a significantly elevated risk of ESKD (hazard ratio 2.28 [95 % confidence interval 1.23-4.22] and 1.75 [1.19-2.57], respectively). Corresponding estimates for CKD were 1.54 (1.14-2.09) and 1.63 (1.38-1.93). Borderline low ABI 0.91-1.00 also showed elevated risk of adverse kidney outcomes after adjustment for demographic variables. Largely consistent results were observed across demographic and clinical subgroups. CONCLUSIONS: Symptomatic PAD and asymptomatic PAD were independently associated with an elevated risk of ESKD and CKD. These results highlight the importance of monitoring kidney function in persons with PAD, even when symptoms are absent.

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.

Anticoagulation in embolic acute limb ischaemia-an observational study.

The management of embolic acute limb ischaemia commonly involves determining aetiology and performing emergency invasive procedures. This detailed study aimed to determine the impact of manipulation of anticoagulation in the aetiology of emboli in acute limb ischaemia and determine the efficacy of primary anticoagulation therapy vs. invasive interventions. Material and methods: Data collection was conducted at a single institution on a cohort of patients presenting consecutively with embolic acute limb ischaemia over one year. Two groups were compared, one receiving anticoagulation as primary therapy with those undergoing invasive treatment as the internal comparison group. Results: A likely haematological causation was identified in 22 of 38 presentations, related to interruption of anticoagulation in cardiac conditions, the majority atrial fibrillation (n=12), or hypercoagulable states (n=10). Limb salvage was pursued in 36 patients employing anticoagulation (n=19) or surgical embolectomy (n=17) as the primary therapy in upper and lower limbs (n=17 vs n=19 respectively). Despite delays often well beyond six hours and a range of ischaemic severity in both groups, 35 of 36 patients achieved full or substantive restoration of function with improved perfusion. Regarding anatomical distribution of arterial disease and therapy, three patients with multi-level disease proceeded to embolectomy following anticoagulation. Embolectomy was undertaken most often for proximal emboli and more profound paralysis. Conclusions: Anticoagulation and coagulopathy are commonly implicated in the aetiology of arterial emboli, with omission of effective anticoagulation in atrial fibrillation being associated in almost 1/3 of presentations. Whilst more profound limb paralysis and proximal or multi-level disease tended to be managed surgically, primary anticoagulation therapy alone or with a secondary embolectomy was effective across the spectrum of ischaemia severity and despite significant delays beyond guideline recommendations.

2024 Guideline for Management of Wounds in Patients With Lower Extremity Arterial Disease: An Executive Summary.

This article is an executive summary of the Wound, Ostomy, and Continence Nurses Society's (WOCN) 2024 Guideline for Management of Wounds in Patients With Lower Extremity Arterial Disease. It is part of the Society's Clinical Practice Guideline Series. This article presents an overview of the systematic process used to update and develop the guideline. It also lists specific recommendations from the guideline for screening and diagnosis, assessment, management, and education of patients with wounds due to lower extremity arterial disease (LEAD). Suggestions for implementing recommendations from the guideline are also summarized. The guideline is a resource for WOC nurse specialists, other nurses, and health care professionals who work with adults who have/or are at risk of wounds due to LEAD. The complete guideline includes the evidence and references supporting the recommendations, and it is available from the WOCN Society's Bookstore (www.wocn.org). Refer to the Supplemental Digital Content Appendix (available at: http://links.lww.com/JWOCN/A123) associated with this article for a complete reference list for the guideline.

Fenofibrate to prevent amputation and reduce vascular complications in patients with diabetes: FENO-PREVENT.

BACKGROUND: The potential preventive effect of fenofibrate on lower extremity amputation (LEA) and peripheral arterial disease (PAD) in patients with type 2 diabetes (T2D) is not fully elucidated. METHODS: We selected adult patients ≥ 20 years of age with T2D from the Korean National Health Insurance Service Database (2009-2012). The fenofibrate users were matched in a 1:4 ratio with non-users using propensity scores (PS). The outcome variables were a composite of LEA and PAD and the individual components. The risks of outcomes were implemented as hazard ratio (HR) with 95% confidence intervals (CI). For safety issues, the risks of acute kidney injury, rhabdomyolysis and resulting hospitalization were analyzed. RESULTS: A total of 114,920 patients was included in the analysis with a median follow-up duration of 7.6 years (22,984 and 91,936 patients for the fenofibrate user and non-user groups, respectively). After PS matching, both groups were well balanced. The fenofibrate group was associated with significantly lower risks of composite outcome of LEA and PAD (HR 0.81; 95% CI 0.70-0.94), LEA (HR 0.76; 95% CI 0.60-0.96), and PAD (HR 0.81; 95% CI 0.68-0.96). The risk of acute kidney injury, rhabdomyolysis, or hospitalization for these events showed no significant difference between the two groups. Subgroup analyses revealed consistent benefits across age groups, genders, and baseline lipid profiles. CONCLUSIONS: This nationwide population-based retrospective observational study suggests that fenofibrate can prevent LEA and PAD in patients with T2D who are on statin therapy.

MicroRNAs in diabetic macroangiopathy.

Diabetic macroangiopathy is a leading cause of diabetes-related mortality worldwide. Both genetic and environmental factors, through a multitude of underlying molecular mechanisms, contribute to the pathogenesis of diabetic macroangiopathy. MicroRNAs (miRNAs), a class of non-coding RNAs known for their functional diversity and expression specificity, are increasingly recognized for their roles in the initiation and progression of diabetes and diabetic macroangiopathy. In this review, we will describe the biogenesis of miRNAs, and summarize their functions in diabetic macroangiopathy, including atherosclerosis, peripheral artery disease, coronary artery disease, and cerebrovascular disease, which are anticipated to provide new insights into future perspectives of miRNAs in basic, translational and clinical research, ultimately advancing the diagnosis, prevention, and treatment of diabetic macroangiopathy.

Diagnostic Potential of Combined Photoplethysmography and Ankle-Brachial Index in Peripheral Arterial Disease: A Duplex Ultrasonography-Based Comparative Study.

BACKGROUND: Although ankle-brachial index (ABI) and photoplethysmography (PPG) have also shown adequate sensitivity in detecting peripheral arterial disease, their diagnostic performance is less reliable in asymptomatic cases or those with high atherosclerotic cardiovascular risks. METHODS AND RESULTS: We evaluated 130 participants using ABI, PPG, and duplex ultrasonography, diagnosing 65 with peripheral arterial disease. From the PPG, we derived 2 parameters: PPG amplitude ratio of the lower-to-upper extremities (PPGratio) and the PPG amplitude of the lower extremity (PPGamp). Sensitivity, specificity, accuracy, and the area under receiver operating characteristic (ROC) curve were calculated for PPG parameters and ABI, and their combination of both methods. Univariate and multivariate logistic regression assessed the prognostic potential of these parameters. ROC analysis revealed optimal cutoff values in diagnosing peripheral arterial disease were 0.417 for PPGratio and "58" for PPGamp. Both PPGratio and PPGamp demonstrated significantly higher sensitivities, 78.4% and 75.7%, respectively, compared with 55.9% for ABI <0.9 (P<0.05). The areas under the ROC curves of combination models, including model 1 (ABI <0.9 and PPGratio), model 2 (ABI <0.9 and PPGamp), and model 3 (ABI <0.9, PPGratio, and PPGamp), exhibited improved performance with areas under the ROC curves of 0.922, 0.922, and 0.931 (all P<0.01) compared with ABI alone (area under the ROC curve, 0.822). Additionally, the PPG parameters, both alone and combined with ABI, were associated with major adverse cardiac events and all-cause mortality after adjusting for other relevant factors. CONCLUSIONS: On the basis of duplex ultrasonography, combining ABI and PPG markedly improves peripheral arterial disease diagnosis in high-risk individuals compared with either method alone and provides crucial insights into major adverse cardiac events and all-cause mortality risks.

Association between aortic calcification and cytokine levels in patients with peripheral artery disease.

Aortic calcification-a marker of advanced atherosclerosis in large arteries-associates with cardiovascular mortality and morbidity. Little is known about the soluble inflamJarmatory profiles involved in large artery atherosclerosis. We investigated the correlation between aortic calcification in the abdominal aorta and cytokine levels in a cohort of peripheral artery disease patients. Aortic calcification index was measured from computed tomography exams and circulating cytokine levels were analyzed from blood serum samples of 156 consecutive patients prior to invasive treatment of peripheral artery disease. The study included 156 patients (mean age 70.7 years, 64 (41.0%) women). The mean ankle-brachial index (ABI) was 0.64 and the mean aortic calcification index (ACI) was 52.3. ACI was associated with cytokines cutaneous T-cell-attracting chemokine CTACK (ß 23.08, SE 5.22, p < 0.001) and monokine induced by gamma-interferon MIG (ß 9.40, SE 2.82, p 0.001) in univariate linear regression. After adjustment with cardiovascular risk factors, CTACK and MIG were independently associated with ACI, ß 17.9 (SE 5.22, p < 0.001) for CTACK and ß 6.80 (SE 3.33, p 0.043) for MIG. CTACK was significantly higher in the patients representing the highest ACI tertile (highest vs. middle, 7.53 vs. 7.34 Tukeys HSD p-value 0.023 and highest vs. lowest tertile 7.53 vs. 7.29, Tukeys HSD p-value 0.002). MIG was significantly higher in the highest tertile versus lowest (7.65 vs. 7.30, Tukeys HSD p-value 0.027). Cytokines CTACK and MIG are associated with higher ACI, suggesting that CTACK and MIG reflect atherosclerotic disease burden of the aorta. This might further suggest the possible association with other cardiovascular morbidities.

Causal association between circulating inflammatory proteins and peripheral artery disease: a bidirectional two-sample Mendelian randomization study.

Introduction: A growing body of research has shown a strong connection between circulating inflammatory proteins and Peripheral artery disease (PAD). However, the causal relationship between circulating inflammatory proteins and PAD is still not fully understood. To investigate this association, we conducted a bidirectional Mendelian randomization study. Materials and methods: Our study utilized genetic variation data obtained from genome-wide association studies (GWAS) datasets. Specifically, the GWAS dataset related to PAD (identifier: finn-b-I9_PAD) included 7,098 cases and 206,541 controls. Additionally, we extracted data on 91 inflammatory proteins from another GWAS dataset (identifiers: GCST90274758-GCST90274848), involving 14,824 participants. To assess the causal relationship between circulating inflammatory proteins and PAD development, we employed methodologies such as inverse variance weighting (IVW), MR Egger regression, and the weighted median approach. Furthermore, sensitivity analyses were conducted to ensure the reliability and robustness of our findings. Results: Two inflammatory proteins were found to be significantly associated with PAD risk: Natural killer cell receptor 2B4 levels (OR, 1.219; 95% CI,1.019~1.457; P=0.03), Fractalkine levels (OR, 0.755; 95% CI=0.591~0.965; P=0.025). PAD had statistically significant effects on 12 inflammatory proteins: C-C motif chemokine 19 levels (OR, 0.714; 95% CI, 0.585 to 0.872; P=0.001), T-cell surface glycoprotein CD5 levels (OR, 0.818; 95% CI, 0.713 to 0.938; P=0.004), CUB domain-containing protein 1 levels (OR, 0.889; 95% CI, 0.809 to 0.977; P=0.015), Fibroblast growth factor 23 levels (OR, 1.129; 95% CI, 1.009 to 1.264; P=0.034), Interferon gamma levels (OR, 1.124; 95% CI, (1.011 to 1.250); P=0.031),Interleukin-15 receptor subunit alpha levels (OR, 1.183; 95% CI,(1.005 to 1.392); P=0.044), Interleukin-17C levels (OR,1.186; 95% CI, (1.048 to 1.342); P=0.007), Interleukin-1-alpha levels (OR, 1.349; 95% CI, (1.032 to 1.765); P=0.029), Interleukin-5 levels (OR, 1.119; 95% CI,(1.003 to 1.248); P=0.043), Latency-associated peptide transforming growth factor beta 1 levels (OR,1.123; 95% CI, (1.020 to 1.236); P=0.018), Matrix metalloproteinase-10 levels (OR, 1.119; 95% CI,(1.015 to 1.233); P=0.024), Signaling lymphocytic activation molecule levels (OR, 0.823; 95% CI, (0.693 to 0.978); P=0.027). Conclusion: Our research expands on genetic studies exploring the strong association between circulating inflammatory proteins and PAD. This discovery has the potential to inform and shape future clinical and basic research endeavors in this area.

Neutrophil-to-lymphocyte ratio in type 2 diabetes patients combined with Lower Extremity Peripheral Artery Disease.

Objective: This study explored the utility of NLR (neutrophil-to-lymphocyte ratio) as a marker to predict Lower Extremity Peripheral Artery Disease (PAD) in the Chinese population, as well as to assess its consistency and diagnostic value with digital subtraction angiography. Methods: Patients were distributed into three groups according to the angiography in lower limb arterial: group L1, plaque with no stenosis; group L2, plaque with luminal stenosis and group L3, total vascular occlusion. Changes in the neutrophil-to-lymphocyte ratio were documented and compared among groups. Results: Compared to group L1, NLR was significantly increased in L2 (1.76 vs 2.35, p=0.037) and L3 (1.76 vs 3.60, p<0.001), with a gradual decrease in ABI (Ankle-Brachial Index, 1.11 vs 1.02 vs 0.94, p<0.001). Those older patients with higher prevalence of hypertension (p=0.002), obesity (p=0.032), or reduced high-density lipoprotein cholesterol (p=0.020) were more likely to develop PAD; higher glycosylated hemoglobin (p=0.045), low-density lipoprotein cholesterol (p=0.006), and systolic blood pressure (p<0.001) levels led to a greater tendency to suffer stenosis or even occlusion; the probability of severe stenosis (>70%) increased to 2.075 times for every 1 increase in NLR, while it was 46.8% for every 0.1 increase in ABI. The optimal NLR cut-off value to predict severe stenosis in PAD was 2.73. Receiver operating characteristic curve analysis of the inflammatory biomarkers and severe stenosis prediction displayed an area under the curve of 0.81. Conclusion: NLR could serve as a new noninvasive and accurate marker in predicting PAD.

Peripheral artery disease risk factors: A focus on lipoprotein(a).

There is a well-established and strong link between high lipoprotein(a) concentration and coronary heart disease, but the evidence regarding peripheral artery disease and carotid atherosclerosis is not as conclusive. This review aims to summarize the relationships between lipoprotein(a), peripheral artery disease and carotid atherosclerosis, in order to try to understand the weight of lipoprotein(a) in determining the development, progression and any complications of atherosclerotic plaque at the carotid and peripheral artery level. There is currently no effective therapy to reduce lipoprotein(a) concentration, but understanding its significance as a vascular risk factor is the starting point to then explore (when effective therapies become available) if there is the possibility, even in patients with peripheral artery disease and carotid atherosclerosis, to achieve better control of the residual vascular risk that is ultimately induced by lipoprotein(a).

Dyslipidemia and lower extremity arterial disease.

INTRODUCTION: Dyslipidemia is an established risk factor for cardiovascular diseases. We aimed to review its role in the pathogenesis of lower extremity arterial disease (LEAD), as well as the effect of lipid-lowering treatment on the progression of LEAD. EVIDENCE ACQUISITION: PubMed/MedLine, EMBASE and Scopus were searched between January 1990 and January 2024 for articles investigating the role of dyslipidemias and hyperlipidemias in the pathogenesis of LEAD. A separate search focused on the effects of lipid-lowering therapy on patients with LEAD. EVIDENCE SYNTHESIS: There is evidence that dyslipidemias play a major role in the development of LEAD. All patients with LEAD should receive intensive lipid-lowering therapy for the reduction not only of claudication symptoms and amputation rates, but also of myocardial infarction and cardiovascular event rates. CONCLUSIONS: Vascular specialists should keep in mind the pivotal role of dyslipidemia in the pathogenesis and progression of LEAD.