RESUMEN

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.

Asunto(s)

RESUMEN

Background: Lower extremity peripheral artery disease (LEAD) is a significant chronic complication of type 2 diabetes mellitus (T2DM) that significantly contributes to disability and mortality. The subtle presentation of LEAD symptoms often leads to underrecognition and misdiagnosis. Therefore, identifying simple and effective evaluation indicators is essential for the early detection and management of LEAD. Insulin resistance is closely associated with diabetes and its complications. However, the specific relationship between insulin resistance-measured by the triglyceride-glucose (TyG) index-and obesity indicators in relation to LEAD remains unclear. Objective: This study aims to investigate the association between the TyG index and its combination with obesity indicators in participants with T2DM and LEAD. Methods: We performed a univariate analysis on 3176 T2DM patients to identify risk factors for LEAD. Patients were then divided into quartiles based on the TyG index combined with various obesity indicators. The chi-square test was used to compare the prevalence of LEAD across these groups. Logistic regression analysis was conducted to examine the association between the TyG index, in combination with different obesity indicators, and the occurrence of LEAD. Finally, we assessed the predictive ability of the TyG index combined with obesity indicators for LEAD by comparing the area under the ROC curve (AUC). Results: The study included 3176 T2DM patients (1691 males and 1485 females) with a mean age of 56.16±10.60 years. Among them, 106 individuals had LEAD. The prevalence of LEAD varied significantly across quartiles of the TyG index, TyG-WC, and TyG-WHR (Q4 > Q3 > Q2 > Q1; P < 0.05). Multiple logistic regression analysis showed that the TyG index, TyG-WC, and TyG-WHR were positively associated with the risk of LEAD in T2DM patients. ROC curve analysis identified the best cutoff values for predicting LEAD: 9.8059 for the TyG index (sensitivity: 49.1%, specificity: 67.9%, AUC: 0.583), 808.8397 for TyG-WC (sensitivity: 70.8%, specificity: 47.8%, AUC: 0.603), and 8.8543 for TyG-WHR (sensitivity: 75.5%, specificity: 44.6%, AUC: 0.607). Conclusion: In T2DM patients, the TyG index, TyG-WHR, and TyG-WC are positively associated with the occurrence of LEAD. TyG-WHR and TyG-WC exhibit a stronger correlation with LEAD compared to the TyG index alone, indicating their superior diagnostic value.

RESUMEN

Sarcopenia was recently reported to be relevant to an increased macro-and microvascular disease risk. Sarcopenia index (SI) has been identified as a surrogate marker for sarcopenia. The aim of the present study was to investigate the association between macro- and microvascular disease and SI in patients with type 2 diabetes mellitus (T2DM). A total of 783 patients with T2DM were enrolled in this cross-sectional study. The SI was calculated by (serum creatinine [mg/dL]/cystatin C [mg/L]) × 100. The subjects were divided into three groups according to SI tertiles: T1 (41.27-81.37), T2 (81.38- 99.55), and T3 (99.56-192.31). Parameters of macro- and microvascular complications, including diabetic retinopathy (DR), micro- and macroalbuminuria (MAU), diabetic peripheral neuropathy (DPN), and lower extremity peripheral artery disease (LEAD) were evaluated. Multivariate logistic regression analysis revealed that when taking the top tertile of SI as a reference, an increasing trend of the prevalence of DR, MAU, DPN, and LEAD were presented (all P for trend  < 0.05), where the OR (95% CI) for DR prevalence was 1.967 (1.252-3.090) in T2, 2.195 (1.278-3.769) in T1, for MAU was 1.805 (1.149-2.837) in T2, 2.537 (1.490-4.320) in T1, for DPN was 2.244 (1.485-3.391) in T2, 3.172 (1.884-5.341) in T1, and for LEAD was 2.017 (1.002-4.057) in T2, 2.405 (1.107-5.225) in T1 (all P < 0.05). Patients with lower SI were more inclined to have an increased risk of macro- and microvascular damage in T2DM population, which may be related to sarcopenia.

Asunto(s)

RESUMEN

Lower-extremity peripheral artery disease (LE-PAD) is a prevalent circulatory disorder with risks of critical limb ischemia and amputation. This study aimed to develop a prediction model for a novel LE-PAD subtype to predict the severity of the disease and guide personalized interventions. Additionally, LE-PAD pathogenesis involves altered immune microenvironment, we examined the immune differences to elucidate LE-PAD pathogenesis. A total of 460 patients with LE-PAD were enrolled and clustered using unsupervised machine learning algorithms (UMLAs). Logistic regression analyses were performed to screen and identify predictive factors for the novel subtype of LE-PAD and a prediction model was built. We performed a comparative analysis regarding neutrophil levels in different subgroups of patients and an immune cell infiltration analysis to explore the associations between neutrophil levels and LE-PAD. Through hematoxylin and eosin (H&E) staining of lower-extremity arteries, neutrophil infiltration in patients with and without LE-PAD was compared. We found that UMLAs can helped in constructing a prediction model for patients with novel LE-PAD subtypes which enabled risk stratification for patients with LE-PAD using routinely available clinical data to assist clinical decision-making and improve personalized management for patients with LE-PAD. Additionally, the results indicated the critical role of neutrophil infiltration in LE-PAD pathogenesis.

RESUMEN

Background: Patients with symptomatic lower-extremity peripheral artery disease (LE-PAD) are prone to serious cardiovascular and limb events. Few studies have evaluated the effect of rivaroxaban-based dual antithrombotic therapy in high-risk patients with LE-PAD in Asian populations. Objectives: To investigate the efficacy and safety of rivaroxaban-based dual antithrombotic therapy in symptomatic patients with LE-PAD. Design: Retrospective cohort study. Methods: This study included patients with LE-PAD treated at the Nanjing Drum Tower Hospital from 1 January 2018 to 31 December 2021. These participants were divided into antiplatelet (APT) or antiplatelet therapy combined with rivaroxaban (RAPT) groups. The efficacy outcomes in this study were the occurrence of major adverse cardiovascular events (MACE), including myocardial infarction, ischemic stroke, or death from cardiovascular causes, and major adverse limb events (MALE), including urgent revascularization, acute limb ischemia, and major amputation. The safety outcomes included major and clinically relevant non-major (CRNM) bleeding. Patients were followed up until the time of death or the end of the study (31 March 2023). Results: We included 1144 patients with LE-PAD (APT: 502 patients; RAPT: 642 patients). The RAPT group had a lower risk of primary composite efficacy outcomes [hazard ratio (HR): 0.40] and a nonsignificant increase in major bleeding risk (HR: 2.33) than the APT group. The RATP group also had a significantly lower risk of secondary efficacy outcomes, including ischemic stroke (HR: 0.41), myocardial infarction (HR: 0.31), cardiovascular death (HR: 0.40), and MALE (HR: 0.65), than the APT group. The CRNM bleeding incidence varied between the two groups (HR: 3.96). Moreover, no significant interactions were observed between the subgroups and treatment groups in the composite efficacy analysis. Conclusion: Rivaroxaban-based dual antithrombotic therapy significantly reduced the occurrence of MACE in patients with LE-PAD without increasing major bleeding events. High-risk patients benefited from the dual antithrombotic therapy.

Background: Serious cardiovascular and limb events are common adverse effects in patients with symptomatic lower-extremity peripheral artery disease (LE-PAD).Few studies have reported the benefits of dual antithrombotic therapy with rivaroxaban in patients with high risk of LE-PAD in Asian populations. Methods: We collected data from in-patients with LE-PAD from January 1, 2018 to December 31, 2021.Depending on the antithrombotic medication administered, we classified the patients into antiplatelet therapy (e.g., aspirin and clopidogrel; APT group) and antiplatelet therapy combined with rivaroxaban (RAPT group) groups.The primary efficacy outcome was major adverse cardiovascular events (MACE), which was a composite of myocardial infarction, ischemic stroke or death from cardiovascular causes. The primary safety outcome was major bleeding.Secondary clinical outcomes included myocardial infarction, ischemic stroke, death from cardiovascular causes, clinically relevant non-major (CRNM) bleeding, and major adverse limb events (MALE), including urgent revascularization, acute limb ischemia, and major amputation.Follow-up continued until death or the end of the study (March 31, 2023). Results: The RAPT group had a lower risk of primary composite efficacy outcome and a non-significant increase in the risk of major bleeding than the APT group.The risk of secondary efficacy was significantly lower in the RAPT group than in the APT groups. The incidence of CRNM bleeding varied between the two groups.The subgroups and treatment groups had no significant interactions with the risk of composite efficacy outcomes. Conclusions: Rivaroxaban-based dual antithrombotic therapy has a clear therapeutic advantage over single antiplatelet therapy in Asian populations and does not increase the risk of major bleeding.Rivaroxaban-based combination therapy reduces the risk of serious adverse cardiovascular and limb events with an acceptable safety profile.

Comparison of rivaroxaban-based dual antithrombotic and antiplatelet therapies for symptomatic patients with lower-extremity peripheral artery disease post-revascularization: a retrospective cohort study.

RESUMEN

Objective: Atherosclerosis expression varies across not only coronary, cerebrovascular, and peripheral arteries but also within the peripheral vascular tree. The underlying pathomechanisms of distinct atherosclerosis phenotypes in lower extremity peripheral artery disease (PAD) is poorly understood. We investigated the association of cardiovascular risk factors (CVRFs) and atherosclerosis distribution in a targeted approach analyzing symptomatic patients with isolated anatomic phenotypes of PAD. Methods: In a cross-sectional analysis of consecutive patients undergoing first-time endovascular recanalization for symptomatic PAD, data of patients with isolated anatomic phenotypes of either proximal (iliac) or distal (infrageniculate) atherosclerosis segregation were extracted. We performed a multivariable logistic regression model with backward elimination to investigate the association of proximal and distal PAD with CVRFs. Results: Of the 637 patients (29% females) with endovascular recanalization, 351 (55%) had proximal and 286 (45%) had distal atherosclerosis. Female sex [odds ratio (OR) 0.33, 95% confidence interval (CI) 0.20-0.54, p = 0.01], active smoking (OR 0.16, 95% CI 0.09-0.28, p < 0.001), and former smoking (OR 0.33, 95% CI 0.20-0.57, p < 0.001) were associated with proximal disease. Diabetes mellitus (DM) (OR 3.25, 95% CI 1.93-5.46, p < 0.001), chronic kidney disease (CKD) (OR 1.18, 95% CI 1.08-1.28, p < 0.001), and older age (OR 1.31, 95% CI 1.06-1.61, p = 0.01) were associated with distal disease. Conclusion: Female sex, particularly in the context of smoking, is associated with clinically relevant, proximal atherosclerosis expression. Our additional findings that distal atherosclerosis expression is associated with DM, CKD, and older age suggest that PAD has at least two distinct atherosclerotic phenotypes with sex-specific and individual susceptibility to atherogenic risk factors.

RESUMEN

PURPOSE: Endovascular therapies (EVTs) for symptomatic lower extremity peripheral artery disease (PAD) are efficient and minimally invasive. However, patients with PAD tend to have high bleeding risk (HBR), and there are limited data regarding the HBR for patients with PAD after EVT. In this study, we investigated the prevalence and severity of HBR, as well as its association with clinical outcomes in the patients with PAD who underwent EVT. MATERIALS AND METHODS: The Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria were applied to 732 consecutive patients with lower extremity PAD post-EVT to assess the prevalence of HBR, and its association with major bleeding events, all-cause mortality, and ischemic events. The ARC-HBR scores (1 point for each major criterion and 0.5 points for each minor criterion) were obtained and the patients were divided into four groups (score: 0-0.5; low risk, score: 1-1.5; moderate risk, score: 2-2.5; high risk, and score: ≥3; very high risk) according to the score. Major bleeding events were defined as Bleeding Academic Research Consortium type-3 or type-5 bleeding, and ischemic events were defined as the composite of myocardial infarction, ischemic stroke, and acute limb ischemia within 2 years. RESULTS: High bleeding risk occurred in 78.8% of the patients. Major bleeding events, all-cause mortality, and ischemic events occurred in 9.7%, 18.7%, and 6.4% of the study cohort, respectively, within 2 years. During the follow-up period, major bleeding events significantly increased with the ARC-HBR score. The severity of the ARC-HBR score was significantly associated with an increased risk of major bleeding events (high risk: adjusted hazard ratio [HR] 5.62; 95% confidence interval [CI]: [1.28, 24.62]; p=0.022; very high risk: adjusted HR: 10.37; 95% CI: [2.32, 46.30]; p=0.002). All-cause mortality and ischemic events also significantly increased with higher ARC-HBR score. CONCLUSIONS: High bleeding risk patients with lower extremity PAD can be at a high risk of bleeding events, mortality, and ischemic events after EVT. The ARC-HBR criteria and its associated scores can successfully stratify HBR patients and assess the bleeding risk in patients with lower extremity PAD who undergo EVT. CLINICAL IMPACT: Endovascular therapies (EVTs) for symptomatic lower extremity peripheral artery disease (PAD) are efficient and minimally invasive. However, patients with PAD tend to have high bleeding risk (HBR), and there are limited data regarding the HBR for patients with PAD after EVT. Post EVT, most of the patients with PAD were classified as having HBR using the Academic Research Consortium for HBR (ARC-HBR) criteria and the rate of bleeding events as well as mortality and ischemic events within 2 years increased as the ARC-HBR score increased in this retrospective study of 732 participants. HBR patients with PAD can be at high risk of not only bleeding events but also mortality and ischemic events in the mid-term. The ARC-HBR criteria and its associated scores can successfully stratify HBR patients and assess the bleeding risk in patients with PAD who underwent EVT.

RESUMEN

Exercise training is an important therapeutic strategy for lower extremity peripheral artery disease (PAD). However, the effects of different exercise frequency on physiological adaptations remain unknown. Thus, this study compared the effects of a 7-week moderate-intensity aerobic training performed either three or five times/week on skeletal muscle gene expression and physical performance in mice with PAD. Hypercholesterolemic male ApoE-deficient mice were subjected to unilateral iliac artery ligation and randomly assigned to sedentary or exercise training regimens either three or five times/week. Physical performance was assessed using a treadmill test to exhaustion. Expression of genes related to glucose and lipid metabolism, mitochondrial biogenesis, muscle fiber-type, angiogenesis, and inflammation was analyzed in non-ischemic and ischemic gastrocnemius muscles by real-time polymerase chain reaction. Physical performance was improved to the same extent in both exercise groups. For gene expression patterns, no statistical differences were observed between three or five times/week exercised mice, both in the non-ischemic and ischemic muscles. Our data show that exercising three to five times a week induces similar beneficial effects on performance. Those results are associated with muscular adaptations that remain identical between the two frequencies.

RESUMEN

INTRODUCTION: Community distress is associated with adverse outcomes in patients with cardiovascular disease; however, its impact on clinical outcomes after peripheral vascular intervention (PVI) is uncertain. The Distressed Communities Index (DCI) is a composite measure of community distress measured at the zip code level. We evaluated the association between community distress, as measured by the DCI, and 24-month mortality and major amputation after PVI. METHODS: We used the Vascular Quality Initiative database, linked with Medicare claims data, to identify patients who underwent initial femoropopliteal PVI between 2017 and 2018. DCI scores were assigned using patient-level zip code data. The primary outcomes were 24-month mortality and major amputation. We used time-dependent receiver operating characteristic curve analysis to determine an optimal DCI value to stratify patients into risk categories for 24-month mortality and major amputation. Mixed Cox regression models were constructed to estimate the association of DCI with 24-month mortality and major amputation. RESULTS: The final cohort consisted of 16,864 patients, of whom 4734 (28.1%) were classified as having high community distress (DCI ≥70). At 24 months, mortality was elevated in patients with high community distress (30.7% vs 29.5%, P = .02), as was major amputation (17.2% vs 13.1%, P <.001). After adjusting for demographic and clinical characteristics, a 10-point higher DCI score was associated with increased risk of mortality (hazard ratio: 1.01; 95% confidence interval: 1.00-1.03) and major amputation (hazard ratio: 1.02; 95% confidence interval: 1.00-1.04). CONCLUSIONS: High community distress is associated with increased risk of mortality and major amputation after PVI.

Asunto(s)

RESUMEN

Lower extremity peripheral artery disease (LEPAD) is a common and serious health-threatening disease. The aim of this study was to evaluate the predictive value of 10-year atherosclerotic cardiovascular disease (ASCVD) risk equations from the Prediction for ASCVD Risk in China (China-PAR) project for incident LEPAD after 6.75 ± 0.13 years of follow-up. A total of 3,595 Chinese participants without baseline ASCVD or LEPAD from a community-based cohort were enrolled in our study. The mean (interquartile range) baseline 10-year China-PAR ASCVD risk was 4.35% (2.24-8.44%), and the incidence of new-onset LEPAD during 6.75 ± 0.13 years was 4.23%. In univariable logistic regression analysis, 10-year China-PAR ASCVD risk was significantly associated with LEPAD incidence (odds ratio [OR] for each 1% increase in the risk score = 1.06, 95% confidence interval [CI]: 1.03-1.08, P < 0.001). After adjusting confounders, the relationship remained significant (OR: 1.09, 95% CI: 1.05-1.1. P < 0.001). Participants with the highest risk (≥10%) had significantly increased risk compared to those with the lowest risk (<5%) (OR = 2.65, 95% CI: 1.15-6.07, P = 0.022). Further interaction analyses showed no evidence of heterogeneity according to sex, age, body mass index (BMI), smoking, drinking, hypertension, diabetes mellitus, dyslipidemia, renal function, waist circumference, and family history. In conclusion, 10-year China-PAR ASCVD risk independently predicted the risk of new-onset LEPAD in a Chinese community-based population, indicating the importance of polyvascular diseases (PVDs) and the intrinsic interactions of its components.

RESUMEN

Lower extremity artery disease (LEAD), caused by atherosclerotic obstruction of the arteries of the lower limb extremities, has exhibited an increase in mortality and morbidity worldwide. The phenotypic variability of LEAD is correlated with its complex, multifactorial etiology. In addition to traditional risk factors, it has been shown that the interaction between genetic factors (epistasis) or between genes and the environment potentially have an independent role in the development and progression of LEAD. In recent years, progress has been made in identifying genetic variants associated with LEAD, by Genome-Wide Association Studies (GWAS), Whole Exome Sequencing (WES) studies, and epigenetic profiling. The aim of this review is to present the current knowledge about the genetic factors involved in the etiopathogenic mechanisms of LEAD, as well as possible directions for future research. We analyzed data from the literature, starting with candidate gene-based association studies, and then continuing with extensive association studies, such as GWAS and WES. The results of these studies showed that the genetic architecture of LEAD is extremely heterogeneous. In the future, the identification of new genetic factors will allow for the development of targeted molecular therapies, and the use of polygenic risk scores (PRS) to identify individuals at an increased risk of LEAD will allow for early prophylactic measures and personalized therapy to improve their prognosis.

Asunto(s)

RESUMEN

BACKGROUND: Frailty has been increasingly identified as a risk factor of adverse outcomes in vascular disease. However, its impact on the survival and amputation in patients with lower extremity peripheral artery disease (PAD) remains controversial. This meta-analysis aimed to examine the value of frailty in predicting all-cause mortality or major amputation in patients with lower extremity PAD. METHODS: PubMed, Embase, Web of Sciences, and Scopus databases (up to April 7, 2022) were comprehensively searched to identify relevant studies that investigated the association between frailty and all-cause mortality or major amputation in patients with lower extremity PAD. The impact of frailty on adverse outcomes was summarized by pooling the fully adjusted hazard ratio (HR) with 95% confidence intervals (CI) using a random effect (DerSimonian-Laird) model. RESULTS: Seven studies reporting on eight articles that involved 122,892 patients were included. The prevalence of frailty ranged from 42% to 80% based on the frailty tool used. Meta-analysis showed that frailty was associated with an increased risk of 30-day all-cause mortality (HR 2.11; 95% CI 1.41-3.15; I2 =47.6%, p = 0.148, Tau-squared=0.058) and long-term all-cause mortality (HR 1.86; 95% CI 1.25-2.76; I2 =76.1%, p = 0.002, Tau-squared=0.118). However, no clear association was observed between frailty and major amputation (HR 1.07; 95% CI 0.83-1.36; I2 =23.0%, p = 0.273, Tau-squared=0.019). CONCLUSION: Frailty independently predicts short and long-term all-cause mortality but not major amputation in patients with lower extremity PAD. Frailty status may play an important role in risk stratification of lower extremity PAD.

Asunto(s)

RESUMEN

Background: Peripheral arterial disease (PAD), coronary artery disease (CAD) and carotid stenosis (CS) are robust predictors of mortality. The value of individual vascular beds in polyvascular disease (PVD) to predict mortality in patients with atherosclerotic burden is not clear. Therefore, we have examined the predictive value of PAD, CAD and CS in patients at intermediate to high risk of cardiovascular (CV) disease. Patients and methods: In our retrospective observational study we analyzed baseline data from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, a monocentric cohort study of 3316 patients referred to coronary angiography. Results: As the number of atherosclerotic vascular beds increased, the hazard ratios (HRs) for both all-cause mortality and CV mortality significantly increased in a multivariate analysis after adjusting for age, sex, body mass index, diabetes mellitus and estimated glomerular filtration rate, with HRs of 1.36 (95%CI: 1.11-1.68), 2.56 (95%CI: 2.01-3.26), 2.84 (95%CI: 1.93-4.17) and 1.56 (95%CI: 1.19-2.06), 2.70 (95%CI: 1.97-3.72), 3.50 (95%CI: 2.19-5.62), respectively. The combination of PAD with either CAD or CS was associated with higher HRs for all-cause (HR 2.81 and 7.53, respectively) and CV (HRs 2.80 and 6.03, respectively) mortality compared with the combination of CAD and CS (HRs 1.94 and 2.43, respectively). The presence of PVD was associated with higher age, systolic blood pressure, pulse pressure (PP; a marker of vascular stiffness), former smoking and inversely with lower eGFR. Conclusions: We show that as the number of atherosclerotic vascular beds increases, all-cause and CV mortality rates increase in parallel. Simultaneous prevalence of PAD is associated with significantly higher all-cause and CV mortality rates compared with CS coexistence. Furthermore, increasing atherosclerotic load may contribute to vascular stiffness and impaired renal function.

Asunto(s)

RESUMEN

BACKGROUND: Altered adipokine secretion in dysfunctional adipose tissue facilitates the development of atherosclerotic diseases including lower extremity peripheral artery disease (PAD). Asprosin is a recently identified adipokine and displays potent regulatory role in metabolism, but the relationship between asprosin and lower extremity PAD remains uninvestigated. METHODS: 33 type 2 diabetes mellitus (T2DM) patients (DM), 51 T2DM patients with PAD (DM + PAD) and 30 healthy normal control (NC) volunteers were recruited and the blood samples were collected for detecting the circulatory asprosin level and metabolomic screening. RNA sequencing was performed using the aorta tissues from the type 2 diabetic db/db mice and human umbilical vein endothelial cells (HUVECs) were treated with asprosin to determine its impact on the endothelial-to-mesenchymal transition (EndMT). RESULTS: The circulating levels of asprosin in DM + PAD group were significantly higher than that of NC group and the DM group. Circulating asprosin level was remarkably negatively correlated with ankle-brachial index (ABI), even after adjusting for age, sex, body mass index (BMI) and other traditional risk factors of PAD. Logistic regression analysis revealed that asprosin is an independent risk factor for PAD and receiver-operator characteristic (ROC) curve determined a good sensitivity (74.5%) and specificity (74.6%) of asprosin to distinguish PAD. Data from metabolomics displayed a typical characteristics of de novo amino acid synthesis in collagen protein production by myofibroblasts in patients with PAD and activation of TGF-ß signaling pathway appeared in the aortic tissue of db/db mice. Asprosin directly induces EndMT in HUVECs in a TGF-ß-dependent manner as TGF-ß signaling pathway inhibitor SB431542 erased the promotional effect of asprosin on EndMT. CONCLUSIONS: Elevated circulatory asprosin level is an independent risk factor of lower extremity PAD and might serve as a diagnostic marker. Mechanistically, asprosin directly induces EndMT that participates in vascular injury via activation of TGF-ß signaling pathway. Trial registration This trial was registered at clinicaltrials.gov as NCT05068895.

Asunto(s)

RESUMEN

Lower extremity peripheral artery disease (PAD) is associated with functional decline. Physical exercise has been proven to be an effective therapeutic strategy for PAD; however the effect of exercise initiated before PAD remains unknown. Here, we investigated the preventive effects of exercise on endurance capacity, hindlimb perfusion, and on polarization profile of circulating monocytes and limb muscle macrophages. ApoE-/- mice were subjected to 5-week running wheel exercise or remained sedentary before induction of hindlimb ischemia. The two groups were thereafter kept sedentary. Exercised mice prior to PAD showed higher exhaustive treadmill running distance and time than sedentary mice. Preventive exercise also increased perfusion, arteriole density, and muscle regeneration in the ischemic hindlimb. Moreover, preventive exercise prevented ischemia-induced increased gene expression of pro-inflammatory M1 macrophages markers and cytokines in the ischemic muscle, while no changes were observed for anti-inflammatory M2 macrophage markers. Flow cytometry analysis showed that the proportion of circulating pro-inflammatory monocyte subtype decreased whereas that of anti-inflammatory monocytes increased with preventive exercise. Overall, we show that exercise initiated before PAD improves endurance performance and hindlimb perfusion in mice probably via inhibition of M1 macrophage polarization and inflammation in the ischemic muscle. Our study provides experimental evidence for a role of regular exercise in primary prevention of PAD.

RESUMEN

Lower extremity peripheral artery disease, or often simply called peripheral artery disease (PAD), is a common cardiovascular disease, as coronary artery disease is. Atherosclerotic disease of the arteries of the lower extremity, or arteriosclerosis obliterans, accounts for the vast majority of PAD today. Rest pain, nonhealing ulcers, and gangrenes associated with chronic ischemia (i.e., Fontaine stage III and IV or Rutherford category 4 to 6) are referred to as chronic limb-threatening ischemia (CLTI), formally called critical limb ischemia (CLI). This narrative review focuses on atherosclerotic PAD, especially CLTI, mainly highlighting its link with diabetes mellitus (DM). This article will first overview the clinical impact of DM in patients with symptomatic PAD and that of symptomatic PAD in patients with DM, followed by the clinical features of CLTI, which will be discussed from a viewpoint of its prognosis, patient profile, onset, and seasonality. DM poses a great clinical impact on CLTI, and vice versa. Patient profile appears different between DM patients complicated with CLTI and the general population with DM. Furthermore, although CLTI is pathologically rooted in atherosclerosis as is acute coronary syndrome (ACS), CLTI has considerably different clinical features compared with ACS. CLTI has an extremely poor prognosis even after revascularization, and there is ample room for improvement in terms of its prognosis. Some measures might be needed in healthcare and clinical settings before revascularization: e.g., DM control and regular ischemia risk evaluation before CLTI onset, proper diagnosis at CLTI onset, and prompt referral to a vascular specialist after CLTI onset, although its evidence is still scanty. Piling up evidence of patients with CLTI, by patients with CLTI, and for patients with CLTI is needed.

RESUMEN

BACKGROUND AND AIMS: Polyvascular disease (PVD) affects approximately 20% of patients with atherosclerosis and is a strong independent risk factor for ischemic outcomes. However, guidelines do not address screening or treatment for PVD, and there have been no PVD-specific trials. We reviewed subgroup analyses of large randomized controlled trials of more intense antithrombotic therapy to determine whether increased intensity of therapy improved ischemic outcomes in patients with PVD. METHODS: MEDLINE, MEDLINE in-Process, EMBASE, and the Cochrane Library were queried for randomized controlled trials larger than 5000 patients evaluating secondary prevention therapies in patients with coronary artery disease or lower extremity peripheral artery disease. RESULTS: Thirteen trials were included ranging in size from 7243 to 27,395 patients. In 9 trials (CHARISMA, TRA 2°P-TIMI 50, PEGASUS-TIMI 54, VOYAGER PAD, TRACER, EUCLID, TRILOGY ACS, PLATO, and COMPASS), patients in the PVD subgroup treated with increased-intensity antithrombotic therapy had similar or greater relative risk reductions for ischemic events in comparison with the general trial cohorts. In four trials (DAPT, THEMIS, APPRAISE-2, and ATLAS ACS 2 TIMI 51), the PVD subgroup had an increased hazard of ischemic events with increased-intensity therapy compared with the general trial cohorts. CONCLUSIONS: More intense antithrombotic therapy in patients with PVD was associated with a similar relative risk reduction for ischemic events compared with patients without PVD. Therefore, patients with PVD benefit from a larger absolute risk reduction because of their higher baseline risk. Future trials in patients with atherosclerotic cardiovascular disease should intentionally include PVD patients to adequately assess treatment options for this under-studied, under-treated population.

Asunto(s)

RESUMEN

Peripheral artery disease of the lower limbs is a chronically progressive disorder characterised by the presence of occlusive lesions in the medium and large arteries that result in symptoms secondary to insufficient blood flow to the lower extremities. It is both a manifestation of systemic atherosclerosis and a marker of increased cardiovascular morbidity and mortality. Because of its highly heterogenous clinical picture, a detailed history and physical assessment, a high degree of suspicion for peripheral artery disease and the use of the ankle-brachial pressure index is essential to identify patients with peripheral artery disease. This will allow early administration of basic pharmacotherapy and lifestyle changes to reduce cardiovascular events, minimise claudication symptoms and enable optimal revascularisation to prevent loss of limb function.

Asunto(s)

RESUMEN

OBJECTIVE: The objective of our study was to compare contrast enhancement on CT angiography (CTA) images of the lower extremity in patients with suspected peripheral artery disease who did not undergo hemodialysis (HD) and patients who were scanned before or after HD. MATERIALS AND METHODS: We divided 287 consecutive patients who underwent CTA of the lower extremity on a 64-MDCT scanner into three groups: group 1 patients (n = 151) were not dependent on HD, group 2 patients (n = 70) were dependent on HD and underwent HD less than 24 hours after CTA, and group 3 (n = 66) were dependent on HD and underwent HD less than 24 hours before CTA. We then compared the CT number in the popliteal artery at the level of the patella on all CTA images. A cardiologist and a radiology technologist visually evaluated the depiction of the descending genicular artery (DGA) on the CTA images and assigned a visualization score. RESULTS: The median CT number was lowest in group 2 patients (373 HU vs 429 [group 1] and 418 [group 3] HU). The score for visualization of the DGA was significantly lower in group 2 than in group 1 (p = 0.02) and group 3 (p = 0.04). CONCLUSION: At CTA, arterial enhancement decreases with the passage of time after HD likely because of the increase in intravascular volume. CTA that is performed within 24 hours after HD generates higher-quality images of the lower extremities than CTA that is performed within 24 hours before HD.

Asunto(s)