Relationship Between Arteriovenous Fistula Stenosis and Circulating Levels of Neutrophil Granule Proteins in Chronic Hemodialysis Patients.

BACKGROUND: Arteriovenous fistula (AVF) stenosis leading to its failure is a major cause of morbidity in hemodialysis patients; however, detailed pathogenesis of AVF stenosis is still under investigation. To date, monocytes/macrophages have been considered pivotal players in chronic inflammation of vascular disease including atherosclerosis and AVF stenosis. However, recent evidence strongly suggests that neutrophils and neutrophil granule proteins are important contributors to vascular disease. The aim of the present study was to evaluate the relationship between AVF stenosis and neutrophil activation by measuring circulating levels of neutrophil elastase (NE) and lactoferrin, enzymes released on neutrophil activation, as well as other inflammation markers including neutrophil counts. METHODS: This was a single-center, prospective observational study conducted on 83 prevalent hemodialysis patients with AVF. Blood levels of biomarkers and sonography (US) measurement were assessed at baseline and 1 year after enrollment. Clinical follow-up continued for one more year (a total of 2 years for each patient) to observe any AVF events. RESULTS: Circulating levels of both NE and lactoferrin positively correlated with the degree of AVF stenosis. Patients with significant AVF stenosis had older AVFs, higher neutrophil-to-lymphocyte ratio (NLR), and higher circulating levels of NE and lactoferrin. On multivariate logistic regression analysis, both circulating levels of NE and NLR remained independent predictors of significant AVF stenosis. CONCLUSIONS: Circulating levels of NE and the NLR were identified as independent predictors of at-risk AVF with significant stenosis. Our data suggest the potential role of neutrophil and innate immunity activation on the development of AVF stenosis.

C-Reactive Protein to Albumin Ratio in Patients With Saphenous Vein Graft Disease.

Atherosclerosis plays an important role in saphenous vein graft disease (SVGD). Previous studies showed that inflammatory blood cells play an active role in this process. C-reactive protein to albumin ratio (CAR) is considered as a novel predictor for cardiovascular risk and an indicator of inflammation. We aimed to assess the relationship between SVGD and CAR. A total of 711 participants with saphenous vein graft (SVG) were included; 348 patients had SVGD and 363 patients had patent (no stenosis) SVG. C-reactive protein to albumin ratio was higher in patients with SVGD (P < .001). There was a significant positive correlation between CAR and the age of SVG (r = 0.123; P = .001) and SYNTAX score (r = 0.568; P < .001). Multivariate logistic regression analyses showed that lymphocyte count, CAR, and SYNTAX score were independent predictors of SVGD (P < .05). C-reactive protein to albumin ratio may be a useful marker after bypass surgery to predict SVGD.

Chitinase-3-like protein 1 is an independent risk factor for the early failure of forearm autologous arteriovenous fistulas in uremic patients.

Chitinase-3-like protein 1 (CHI3L1) has been introduced as a marker of inflammation in different diseases, which can promote cell proliferation and differentiation. It has also been demonstrated that elevated serum CHI3L1 concentration can independently predict all-cause mortality in uremic patients. However, the impact of CHI3L1 on the early failure of autologous arteriovenous fistulas (AVFs) in uremic patients remains unknown. We conducted a prospective observational cohort study of 109 uremic patients (mean age 53.2 ± 14.7 years, 67.9% males), who received forearm AVF surgery, and were consecutively enrolled with a median follow-up time of 15 months. The early failure was defined as a fistula that never developed adequately for dialysis or that failed within the first 3 months of use. Serum CHI3L1 concentration was determined by the ELISA method. Among 109 uremic patients, 24 patients had AVF failure. The optimal cutoff value based on the receiver operating characteristics analysis of CHI3L1 was 122.6 ng/mL, with the area under the curve of 0.73 (P = 0.001). The Kaplan-Meier survival analysis demonstrated that patients with CHI3L1 < 122.6 ng/mL had better AVF patency than patients with CHI3L1 ≥ 122.6 ng/mL (Log-rank test, P = 0.001). Multivariable Cox proportional hazards regression analysis showed that baseline CHI3L1 level (≥ 122.6 ng/mL vs. < 122.6 ng/mL) was significantly associated with AVF failure after adjustment for confounders (adjusted hazard ratio [HR], 3.67; 95% CI, 1.44-9.36). The study demonstrated that Increased baseline serum level of CHI3L1 is independently associated with higher risk of the early failure of forearm AVFs.

Evaluation of the Effect of Crosslinking Method of Poly(Vinyl Alcohol) Hydrogels on Thrombogenicity.

PURPOSE: Crosslinked poly(vinyl alcohol) (PVA) is a biomaterial that can be used for multiple cardiovascular applications. The success of implanted biomaterials is contingent on the properties of the material. A crucial consideration for blood-contacting devices is their potential to incite thrombus formation, which is dependent on the material surface properties. The goal of this study was to quantify the effect of different crosslinking methods of PVA hydrogels on in vitro thrombogenicity. METHODS: PVA was manufactured using three different crosslinking methods: 30% sodium trimetaphosphate (STMP), three 24 h freeze-thaw cycles (FT), and 2% glutaraldehyde-crosslinked (GA) to produce STMP-PVA, FT-PVA and GA-PVA, respectively. Expanded polytetrafluoroethylene (ePTFE) was used as a clinical control. As markers of thrombus formation, the degree of coagulation factor (F) XII activation, fibrin formation, and platelet adhesion were measured. RESULTS: The GA-PVA material increased FXII activation in the presence of cofactors compared to vehicle and increase platelet adhesion compared to other PVA surfaces. The STMP-PVA and FT-PVA materials had equivalent degrees of FXII activation, fibrin formation and platelet adhesion. CONCLUSION: This work supports crosslinker dependent thrombogenicity of PVA hydrogels and advances our understanding of how the manufacturing of a PVA hydrogel affects its hemocompatibility.

Patency Rates After Successful Arteriovenous Fistula Thrombectomy: Relevance of the Flow/d-Dimer Ratio in the Decision-Making.

OBJECTIVES: Surgical thrombectomy for acute arteriovenous fistula (AVF) thrombosis is one of the primary salvage intervention. The independent risk factors affecting the patency of AVF after a successful thrombectomy are yet unknown. Here, the author aimed to report the results of surgically corrected AVFs and the independent risk factors which may cause early failure following the surgical salvage. METHODS: The study cohort comprised 24 patients who had acute AVF thrombosis and underwent successful surgical thrombectomy in the first 24 to 48 hours between January 2016 and April 2020 in our center. The study group was divided into patients with recurrent AVF thrombosis (n = 11, 45.8%) and without recurrent AVF thrombosis (n = 13, 54.1%) following surgical thrombectomy with a follow-up of 22.4 ± 6.8 months. Postthrombectomy primary and secondary patency of AVF were also evaluated. RESULTS: The mean age of the cohort was 58.1 ± 15.2 years. A simple thrombectomy was performed for all cases. Only 2 cases have required a revision at the anastomosis due to severe intimal hyperplasia. Postthrombectomy primary patency rate was 45.5% for 18 months. Receiver operating characteristic analysis was performed with a resulting area under the curve value of 0.81 (95% CI: 0.35-0.94, P = .006) for flow (mL)/d-dimer (ng/mL) <0.63 in predicting recurrent AVF thrombosis following surgical thrombectomy. CONCLUSIONS: Flow (mL)/d-dimer (ng/mL) <0.63 was independent predictor of recurrent thrombosis (RT) of a surgically salvaged AVF. The patients at risk for RT or who may benefit from further intervention should be identified with predictive parameters.

The relationship between neutrophil-lymphocyte ratio and in-stent restenosis in superficial femoral artery.

The present study aimed to investigate the relationship between an increase in the pre- and post-operative neutrophil-lymphocyte ratio (NLR) and superficial femoral artery in-stent restenosis (ISR) rate. We recruited 199 patients that underwent superficial femoral artery stenting for lower extremity arteriosclerosis obliterans at our hospital from March 2015 to July 2018. Patients were divided into two groups according to the occurrence of ISR within 1 year (group 1, ISR and group 2, Non-ISR). The after NLR (NLRafter) and NLR change ratio (NLRratio) (P<0.001) were significantly higher in group 1. A NLRafter > 4.3 was associated with an odds ratio of 1.946 (95% CI [1.51-2.50]; P<0.001) for the presence of ISR. A NLRratio > 37.5% was associated with an odds ratio of 3.6 (95% CI [2.03-6.36]; P<0.001) for occurrence of ISR. A NLRafter level > 4.3 had 75% sensitivity and 76% specificity for the prediction of ISR, as identified by the ROC curve. A NLRratio level > 37.5% predicted ISR with 77% sensitivity and 60% specificity. Multivariate logistic regression analysis demonstrated that NLRratio was the strongest independent predictor of ISR (P<0.001). In conclusions, NLRratio could be used as a prognostic marker in superficial femoral artery stents.

Association of Microvesicles With Graft Patency in Patients Undergoing CABG Surgery.

BACKGROUND: Graft patency is one of the major determinants of long-term outcome following coronary artery bypass graft surgery (CABG). Biomarkers, if indicative of the underlying pathophysiological mechanisms, would suggest strategies to limit graft failure. The prognostic value of microvesicles (MVs) for midterm graft patency has never been tested. OBJECTIVES: The aim of this study was to evaluate whether MV pre-operative signature (number, cellular origin, procoagulant phenotype) could predict midterm graft failure and to investigate potential functional role of MVs in graft occlusion. METHODS: This was a nested case-control substudy of the CAGE (CoronAry bypass grafting: factors related to late events and Graft patency) study that enrolled 330 patients undergoing elective CABG. Of these, 179 underwent coronary computed tomography angiography 18 months post-surgery showing 24% graft occlusion. Flow cytometry MV analysis was performed in 60 patients (30 per group with occluded [cases] and patent [control subjects] grafts) on plasma samples collected the day before surgery and at follow-up. RESULTS: Before surgery, cases had 2- and 4-fold more activated platelet-derived and tissue-factor positive MVs respectively than control subjects. The MV procoagulant capacity was also significantly greater. Altogether this MV signature properly classified graft occlusion (area under the curve 0.897 [95% confidence interval: 0.81 to 0.98]; p < 0.0001). By using an MV score (0 to 6), the odds ratio for occlusion for a score above 3 was 16.3 (95% confidence interval: 4.1 to 65.3; p < 0.0001). CONCLUSIONS: The pre-operative signature of MVs is independently associated with midterm graft occlusion in CABG patients and a cumulative MV score stratifies patients' risk. Because the MV signature mirrors platelet activation, patients with a high MV score could benefit from a personalized antiplatelet therapy.

Association Between Plasma Trimethylamine N-oxide and Neoatherosclerosis in Patients With Very Late Stent Thrombosis.

BACKGROUND: Trimethylamine N-oxide (TMAO) has been shown to promote the development of atherosclerosis. However, the relationship between plasma TMAO and neoatherosclerosis, an important underlying mechanism of very late stent thrombosis (VLST), is unknown. METHODS: This post hoc study investigated the association between TMAO and neoatherosclerosis in 2 independent cohorts. These included a control group of 50 healthy volunteers and a study cohort of 50 patients with VLST who presented with ST-segment elevation myocardial infarction and underwent optical coherence tomography examination. Of the 50 patients with VLST, 23 had neoatherosclerosis and 27 did not have neoatherosclerosis. Patients with neoatherosclerosis were further divided into 2 subgroups, including 14 patients with plaque rupture and 9 without plaque rupture. RESULTS: The plasma TMAO levels, detected using mass spectrometry, were significantly higher in patients with VLST than in healthy individuals (median [interquartile range], 2.50 [1.67-3.84] vs 1.32 [0.86-2.44] µM; P < 0.001). Among the patients with VLST, the plasma TMAO levels were significantly higher in patients with neoatherosclerosis than in those without neoatherosclerosis (3.69 [2.46-5.29] vs 1.96 [1.39-2.80] µM; P < 0.001). In addition, in patients with neoatherosclerosis, patients with plaque rupture had significantly higher plasma TMAO concentrations than those without plaque rupture (4.51 [3.41-5.85] vs 2.46 [2.05-3.55] µM; P = 0.005). Multivariate analysis indicated that TMAO was an independent predictor of neoatherosclerosis (odds ratio, 3.41; 95% confidence interval, 1.59-7.30; P = 0.002). Moreover, the area under the receiver operating characteristic curve for TMAO, differentiated by neoatherosclerosis, was 0.85. CONCLUSIONS: Plasma TMAO was significantly correlated with neoatherosclerosis and plaque rupture in patients with VLST.

Oral Charcoal Adsorbents Attenuate Neointima Formation of Arteriovenous Fistulas.

Chronic kidney disease (CKD) accelerates the development of neointima formation at the anastomosis site of arteriovenous (AV) fistulas. Accumulation of certain uremic toxins has a deleterious effect on the cardiovascular system. The oral charcoal adsorbent, AST-120, reduces circulating and tissue uremic toxins, but its effect on neointima formation at an AV fistula is unknown. To understand the effect of CKD and AST-120 on neointima formation, we created AV fistulas (common carotid artery to the external jugular vein in an end-to-side anastomosis) in mice with and without CKD. AST-120 was administered in chow before and after AV fistula creation. Administration of AST-120 significantly decreased serum indoxyl sulfate levels in CKD mice. CKD mice had a larger neointima area than non-CKD mice, and administration of AST-120 in CKD mice attenuated neointima formation. Both smooth muscle cell and fibrin components were increased in CKD mice, and AST-120 decreased both. RNA expression of MMP-2, MMP-9, TNFα, and TGFß was increased in neointima tissue of CKD mice, and AST-120 administration neutralized the expression. Our results provided in vivo evidence to support the role of uremic toxin-binding therapy on the prevention of neointima formation. Peri-operative AST-120 administration deserves further investigation as a potential therapy to improve AV fistula patency.

High low-density lipoprotein cholesterol level is the independent risk factor of primary patency rate of arteriovenous fistula.

OBJECTIVES: An arteriovenous fistula is the first choice of vascular access in dialysis patients. However, the correlations between patient factors and the arteriovenous fistula patency rate remain unclear. Therefore, we examined the effect of dialysis patient factors on arteriovenous fistula patency rate. METHODS: This study included 101 patients who received maintenance dialysis and used arteriovenous fistula for vascular access at Atami Hospital, International University of Health and Welfare in July 2018. A retrospective review was performed from the time of arteriovenous fistula creation to July 2018, and the primary and secondary arteriovenous fistula patency rates were investigated. The patency rate was calculated using the Kaplan-Meier method, and risk factor analysis was performed using Cox proportional hazards regression analysis. RESULTS: The primary patency rate of arteriovenous fistula was 71.2% at one year and 43.0% at five years, and the secondary patency rate was 92.7% at one year and 79.8% at five years. In the multivariate analysis, high low-density lipoprotein cholesterol (LDL-C) level and a history of diabetes were considered significant risk factors (HR 1.023, p value <0.01 and HR 2.550, p value <0.01, respectively). A log rank test was conducted on the groups of patients with LDL <90 mg/dl and LDL ≥90 mg/dl, and the <90 mg/dl group resulted in a good primary patency rate (p value 0.0327). CONCLUSIONS: High LDL-C level was considered the independent risk factors of arteriovenous fistula primary patency rate.

Mean Platelet Volume Does Not Predict Restenosis After Carotid Artery Stenting in Whites.

Background and Purpose- Mean platelet volume (MPV) indicates platelet activity possibly affecting patient's risk for progressive atherosclerotic disease. A recent study identified elevated MPV as a predictor of in-stent restenosis (ISR) after carotid artery stenting (CAS) in a Chinese population. However, the role of MPV on the development of ISR following CAS in whites is yet unknown. Methods- We retrospectively identified all consecutive patients who underwent CAS for atherosclerotic disease at our center from 2005 to 2017. All patients were followed clinically and by duplex sonography at 1, 3, and 6 months and annually after CAS. ISR was defined as ≥50% stenosis (NASCET [North American Symptomatic Carotid Endarterectomy Trial] criteria) in the treated vessel. MPV was assessed before CAS, at last follow-up and at the time of ISR detection. Results- Of 392 patients with CAS (mean age 68.5±9.5 years, 26.8% women, 42.3% symptomatic stenosis), 54 had ISR after a mean follow-up time of 32 months. Baseline MPV was not different in ISR compared with non-ISR patients (10.7 versus 10.6 fL, P=0.316). MPV levels did also not change from baseline to ISR detection (P=0.310) and were not associated with recurrent stroke or vascular events (P>0.5). Multivariable analysis identified active smoking as the sole risk factor for carotid ISR (odds ratio, 2.53 [95% CI, 1.21-5.29]). Conclusions- We did not identify MPV as a risk factor for ISR after CAS in whites. Smoking cessation is an important target to avoid this complication.

Relationship of arteriovenous fistula stenosis and thrombosis with the platelet-lymphocyte ratio in hemodialysis patients.

BACKGROUND: The platelet-lymphocyte ratio, which was reported to have a strong relationship with chronic inflammation and thrombosis, is a useful biomarker. The purpose of this study was to evaluate the relationship between the platelet-lymphocyte ratio, arteriovenous stenosis, and thrombosis in patients with chronic renal failure. METHODS: Patients who were referred to our interventional radiology department due to arteriovenous fistula dysfunction from dialysis units between August 2015 and December 2018 were retrospectively reviewed. In the study, 95 patients with arteriovenous fistula access problems were included. Patients were divided into two groups: stenosis (n = 52) and thrombosis (n = 43). Thirty-six subjects with a patent left radiocephalic arteriovenous fistula proven by both color Doppler ultrasonography and clinically were added to the control group. Blood samples were obtained on the same day before the fistulography. RESULTS: Platelet counts, lymphocyte counts, and platelet-lymphocyte ratio were found to be significantly different between the three groups. After the Bonferroni post hoc analysis, there was a significant difference between the stenosis and control group (p = 0.017), and the thrombosis and control group (p < 0.001) in terms of the platelet-lymphocyte ratio. No significant difference for any parameter was found between stenosis and thrombosis group. CONCLUSION: High levels of the platelet-lymphocyte ratio may be a supportive finding of arteriovenous fistula stenosis and thrombosis and can be taken into consideration during hemodialysis-dependent patients' follow-up.

Plasma D-Dimer Level and the Failure of Forearm Autologous Arteriovenous Fistula in Patients With End-Stage Renal Disease.

Failed autologous arteriovenous fistula (AVF) is a major issue in the creation of functional hemodialysis vascular access. To date, the relationship between D-dimer and AVF failure is still uncertain. Hence, we conducted a retrospective cohort study to explore the patency rate of forearm AVFs and to clarify whether plasma D-dimer level can predict the failure of AVFs. In this study, 290 ESRD patients (the mean age 54.1 ± 14.6 years, 63.8% of them were males) receiving forearm AVFs surgery were consecutively enrolled with a median follow-up time of 34 months. Primary patency rates and risk factors associated with AVFs failure were explored by the Kaplan-Meier method or Cox proportional hazards model. Patients were divided into two groups based on the median level of D-dimer (group 1 <1.1 mg/L and group 2 ≥1.1 mg/L). The Kaplan-Meier survival analysis demonstrated that the patency of AVF in group 1 was similar in group 2, which were 92.4% versus 88.9%, 84.8% versus 84.0%, 80.0% versus 79.2%, 76.7% versus 78.5%, and 76.7% versus 78.5% at 12, 24, 36, 48, and 60 months (Log-rank test, P = 0.8), respectively. In the crude analysis, D-dimer (per 1 mg/L increase) was independently associated with AVFs failure, with OR of 1.08 (95% CI, 1.02-1.15). However, after adjusting for potential confounders, the D-dimer (per 1 mg/L increase) was not associated with the AVFs failure (OR = 1.06, 95% CI = 0.99-1.13). This study did not find that the plasma D-dimer level can predict the failure of forearm AVFs.

Dimethylarginine Dimethylaminohydrolase 1 Polymorphisms and Venous Intimal Hyperplasia in Hemodialysis Patients.

BACKGROUND: After angioplasty, veins are more prone to intimal hyperplasia than arteries. Veins tend to produce less nitric oxide (NO), which could lead to endothelial dysfunction. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase and contributes to cardiovascular disease. In humans, dimethylarginine dimethylaminohydrolase 1 (DDAH1) is the major enzyme for ADMA degradation. In this study, we aim to determine whether venous intimal hyperplasia in hemodialysis (HD) vascular access is influenced by common polymorphisms in the DDAH1 genes. METHODS: This is a prospective observational cohort study. A total of 473 HD patients referred for the angioplasty of vascular access were enrolled. There were 190 arteriovenous grafts (AVG) and 283 arteriovenous fistulas (AVF). The follow-up lasted for 2 years after the interventions. Seven single nucleotide polymorphisms (SNPs) in DDAH1 were genotyped and ADMA were measured at baseline. The primary outcome was restenosis after angioplasty. RESULTS: Among the 7 SNPs, plasma ADMA levels were significantly different in DDAH1 rs233112 (GA + GG vs. AA, 0.86 ± 0.23 vs. 0.82 ± 0.19 µM, p = 0.03) and rs1498373 (CT + TT vs. CC, 0.87 ± 0.23 vs. 0.82 ± 0.20 µM, p = 0.02) genotypes. The AVF group with GG + GA genotype of rs233112 and CT + TT genotype of rs1498373 had higher risks of early restenosis at 3 months. In the AVG group, only GG + GA genotype of rs233112 was associated with early restenosis. A combined analysis of AVG and AVF groups showed that patients with rs233112 GA + GG genotype and rs1498373 CT + TT genotype had higher risks of early restenosis (both p < 0.001). The multivariate analysis results showed that the association of these genotypes with early restenosis is independent of clinical, access, or biochemical factors. CONCLUSIONS: Our findings suggest that certain DDAH1 polymorphisms modulate circulating ADMA levels and are associated with venous intimal hyperplasia.

C-reactive protein as a prognostic risk factor for loss of arteriovenous fistula patency in hemodialyzed patients.

BACKGROUND: Inflammation is a cardiovascular risk factor in hemodialysis patients, but its influence on vascular access patency is still debatable. Our prospective study investigated this issue. METHODS: A total of 258 patients receiving an arteriovenous fistula (AVF) between 2006 and 2016 at the Municipal Hospital Arad were included. Demographic, clinical, and laboratory characteristics were collected at the time of creation of the AVF. The primary study end point was AVF patency loss, defined as an event occurring at least 2 months after AVF formation and requiring surgical revision or replacement of the fistula. The patients were followed up for a median time of 26 months. RESULTS: In our group, the mean age was 59.7 ± 13.2 years (median, 62 years), and 60.1% were male. During follow-up, 134 patients (51.9%) maintained AVF patency, whereas 124 (48.1%) lost AVF patency within a mean time of 23.3 ± 28.1 months (median, 10.5 months). We found that age (hazard ratio [HR], 1.015; P = .035) and C-reactive protein (CRP) level (HR, 1.17; P < .0001) were associated with a higher risk of loss of AVF patency. The protective factors for AVF patency were autosomal dominant polycystic kidney disease (HR, 0.336; P = .009), pre-emptive AVF (HR, 0.648; P = .031), and higher level of triglycerides (HR, 0.998; P = .035). In the multivariate adjusted Cox model, CRP level remained an independent predictor for loss of AVF patency (HR, 1.17; 95% confidence interval, 1.1-1.3; P < .0001). CONCLUSIONS: In our study, CRP level was an independent predictor of AVF patency loss, whereas better AVF survival was independently associated with autosomal dominant polycystic kidney disease and pre-emptive AVF. As a simple noninvasive marker of chronic inflammation, CRP level may be a useful tool to predict AVF outcomes. Further research is needed to assess the protective effects of inflammation reduction on AVF survival.

Restenosis is associated with prothrombotic plasma fibrin clot characteristics in endovascularly treated patients with critical limb ischemia.

INTRODUCTION: Hypolysible fibrin clots composed of tightly packed fibers characterize patients with peripheral artery disease (PAD) especially those with critical limb ischemia (CLI). Little is known about the impact of a prothrombotic clot phenotype on restenosis following endovascular revascularization in CLI. The goal of this study was to compare fibrin clot properties and their determinants in CLI patients with restenosis after endovascular treatment (ET) and those free of this complication. METHODS: 85 patients with CLI and restenosis within 1 year after ET on optimal pharmacotherapy and 47 PAD control patients without restenosis were included into the study. Plasma fibrin clot permeability (Ks, a measure of the average pore size in the fibrin network) and clot lysis time (CLT) with its potential determinants were determined. During follow-up, the composite endpoint including re-intervention, amputation and death was assessed. RESULTS: Compared with the control group, patients with restenosis had reduced Ks (- 9.5%, p < 0.001), prolonged CLT (+ 12.4%, p = 0.003), higher thrombin generation (+ 7.9%, p < 0.001) and elevated von Willebrand factor (vWF) antigen (+ 14.2%, p < 0.001). During a 24 months follow-up the composite endpoint occurred in 54 CLI patients with restenosis (63.5%) and nine control patients (19.1%, p < 0.001) with no association with baseline Ks and CLT. CONCLUSION: The increased thrombin formation and unfavorable fibrin clot properties occur in patients with CLI who experienced restenosis despite optimal endovascular and pharmacological therapy.

Effects of aspirin resistance and mean platelet volume on vascular access failure in hemodialysis patients.

BACKGROUND/AIMS: Maintaining the patency of vascular access (VA) in hemodialysis (HD) patients is important and can be life-saving. We investigated the effects of aspirin resistance and mean platelet volume (MPV) on VA failure in HD patients. METHODS: We enrolled 163 patients on maintenance HD. VA failure was defined as thrombosis or a decrease of > 50% of the normal vessel diameter, as revealed by angiography. RESULTS: Aspirin resistance was observed in 17 of 109 patients in whom this parameter was measured, and was not significantly associated with VA failure (p = 0.051). The mean MPV was 9.15 ± 0.05 fL. The 163 patients were grouped by the median MPV value (9.08 fL) at baseline; patients with higher MPVs (n = 82) had lower platelet counts (p = 0.002) and albumin levels (p = 0.009). During 34 months of follow-up, 65 VA failures (39.9%) occurred. The Kaplan-Meier curve revealed significant differences between the two groups in terms of cumulative VA failure (54.1% vs. 35.3%, p = 0.018). On multivariate analysis, the MPV (hazard ratio [HR], 1.794; 95% confidence interval [CI], 1.066 to 3.020; p = 0.028), platelet count (HR, 1.003; 95% CI, 1.001 to 1.006; p = 0.01), and smoking status (HR, 1.894; 95% CI, 1.019 to 3.519; p = 0.043) independently predicted VA failure. CONCLUSION: A high MPV was associated with an increased risk of VA failure, whereas aspirin resistance showed only a weak association. The MPV may predict VA survival in HD patients.

Imbalance of coagulation and fibrinolysis can predict vascular access failure in patients on hemodialysis after vascular access intervention.

OBJECTIVE: For patients with end-stage renal disease on hemodialysis, the durability of vascular access (VA) is still far from optimal, and access survival after intervention for access failure is an important aspect. Procoagulant status is a leading cause of access failure. Coagulation-fibrinolysis imbalance can occur in hemodialyzed patients, but the influence of the imbalance has not been fully elucidated. METHODS: We prospectively examined coagulation-fibrinolysis balance to assess the risk of access failure after the intervention of revascularization in a cohort of 462 hemodialysis patients. Thrombin-antithrombin complex (TAT) and plasmin-α2-plasmin inhibitor complex (PIC) are markers for coagulation and fibrinolysis. Median follow-up was 243 days. The end point was clinical access failure: revascularization or access revision. The survival curve for VA patency was assessed using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards regression models that allowed adjustment for baseline differences in age, sex, dialysis vintage, diabetes mellitus, and various factors (quantity of blood flow, prothrombin time-international normalized ratio, fibrin degradation products, C-reactive protein, interleukin-6, tumor necrosis factor-α, and pentraxin-3) were used. RESULTS: The 162 patients who reached an end point had smaller access flow volume and smaller percentage of arteriovenous fistula and higher TAT/PIC ratio. Kaplan-Meier analysis indicated that the patients with elevated TAT/PIC ratio showed poorer outcome (P < .001). On Cox regression modeling, elevated TAT/PIC was an independent risk factor for access failure (hazard ratio, 1.58; P = .03). CONCLUSIONS: Our results suggest that coagulation-fibrinolysis imbalance is a significant risk factor for access failure and may predict VA failure in hemodialyzed patients after access intervention.

Impact of Point-of-Care Platelet Function Testing Among Patients With and Without Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents (from the ADAPT-DES Study).

We sought to examine if the risk conferred by high on-treatment platelet reactivity (HPR) varies based upon clinical presentation. We examined the relation between HPR (P2Y12 reaction units >208) and adverse ischemic and bleeding events among patients with and without acute coronary syndromes (ACS) from ADAPT-DES; 51.7% of patients had ACS. After clopidogrel loading, ACS patients had higher P2Y12 reaction units and a greater prevalence of HPR based on VerifyNow P2Y12 assay. Of 92 definite or probable stent thrombosis (ST) events at 2 years, 65.2% occurred among patients with ACS. HPR was independently associated with ST in ACS patients (adjusted hazard ratio 2.29, 95% confidence interval 1.32 to 3.98) but not with clinically relevant bleeding. Although no statistical interactions between ACS status and these associations were observed, non-ACS patients exhibited an attenuated association between HPR and ST, and an inverse association between HPR and clinically relevant bleeding. HPR was similarly associated with myocardial infarction, but not with overall mortality in ACS and non-ACS patients. In conclusion, the majority of ST events in the 2 years after drug-eluting stent placement occurred in ACS patients; HPR was strongly associated with ST in these patients. These data support current recommendations for using more potent antiplatelet therapies in ACS patients.