Glycemic Variability as a Predictor of Graft Failure Following Infrainguinal Bypass for Peripheral Arterial Disease: A Retrospective Cohort Study.

BACKGROUND: Glycemic variability (GV), measured as the change in visit-to-visit glycated hemoglobin (HbA1c), increases the risk of multiple adverse outcomes. However, the impact of GV on graft patency following infrainguinal bypass (IIB) is unknown. A retrospective cohort study was undertaken to assess the impact of GV on graft patency. METHODS: A 3-year single-center retrospective case notes analysis of all people undergoing IIB between 2017 and 2019. Rutherford stage, graft conduit, level of bypass, procedure details, baseline demographics, comorbidities, and GV were assessed. Time to reintervention, ipsilateral amputation, or death was recorded to determine primary patency (PP). RESULTS: One hundred six IIB outcomes were analyzed: mean (± standard deviation) age 68.0 (9.2) years; 69 (65.1%) male, 37 (33.9%), 75 (70.8%) had diabetes mellitus; and 46 (43.4%) underwent elective procedures. GV > 9.1% was associated with significantly lower median PP than GV < 9.1%, 198 (97-753.5) vs. 713 (166.5-1,044.5) days (P = 0.045). On univariate analysis, GV > 9.1% vs. < 9.1% was significantly associated with PP (hazard ratio [HR] 1.85 [confidence interval {CI} 1.091-3.136], P = 0.022). Bypass level was also a univariate predictor, with below knee bypasses (HR 2.31 [CI 1.164-4.564], P = 0.017), and tibial (HR 2.00 [CI 1.022-3.090], P < 0.043) having lower PP than above knee bypasses. On multivariate adjustment, GV > 9.1% and level of bypass remained independent predictors of PP, HR 1.96 (95% CI: 1.12-3.42, P = 0.018) and HR 2.54 (95% CI: 1.24-5.22, P = 0.011), respectively. CONCLUSIONS: GV is an independent predictor of PP following infrainguinal bypass, thus optimizing GV should be a therapeutic target.

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.

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.

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.

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.

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.

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.

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.

Calcium phosphate product level as a predictor for arteriovenous fistula re-operations in patients with chronic renal failure.

OBJECTIVES: There is an increased calcium phosphate product level causing the formation of calcification in the arterial wall and thus decreased quality of fistula in patients with chronic renal failure. The purpose of our study is to verify the relationship between arteriovenous fistula re-operation and high calcium phosphate product level. METHODS: Seventy-nine consecutive patients with chronic renal failure between April 2016 and February 2018 were included in the study. Patients having calcium phosphate product level ≥50 mg2/dl2 were defined as group 1, whereas those having <50 mg2/dl2 were defined as group 2. Primary outcome of interest was the need for re-operation during the follow-up and to determine the risk factors for re-operation. To determine independent predictors for re-operation, multivariate logistic regression model was used. RESULTS: The rates of redo and tredo operation were significantly higher in group 1 compared to group 2 ( p = 0.01 and 0.04). In multivariate analysis, phosphate (OR: 1.84, 95% CI: 1.00-3.40, p = 0.05) and triglyceride (OR: 1.01, 95% CI: 1.00-1.02, p = 0.04) levels for redo operation and calcium phosphate product level (OR: 1.11, 95% CI: 1.01-1.22, p = 0.03) for tredo operation were found to be independent predictors. CONCLUSIONS: High calcium phosphate product level leads to increased risk of arteriovenous fistula re-operation by causing arterial stiffness in this patient group. Additionally, these re-operations place additional burden on morbidity and cost efficacy. Thus, we recommend keeping the calcium phosphate product level at the optimal level in these patients to avoid both the risk of arteriovenous fistula re-operation and the other cardiovascular problems.

Mean Platelet Volume as a Predictor for Restenosis After Carotid Angioplasty and Stenting.

BACKGROUND AND PURPOSE: Platelet aggregation plays a vital role in the development of in-stent restenosis (ISR) after carotid angioplasty and stenting (CAS). Mean platelet volume (MPV) has been suggested as an index of platelet reactivity. This study aimed to investigate the association between MPV and ISR in CAS patients. METHODS: A total of 261 patients with CAS were enrolled. MPV was measured before CAS procedure. Digital subtraction angiography, computed tomographic angiography, or duplex ultrasonography was performed at 6 months and annually after the procedure. ISR was defined as ≥50% stenosis in the treated lesion. Cox regression was used to identify predictors of ISR after CAS. RESULTS: Of the 261 patients with CAS, 46 (17.6%) were determined with ISR during a mean follow-up of 12.1±16.1 months (range, 2.1-120.7). On multivariate analysis, baseline MPV >10.1 fL (hazard ratio, 3.20; 95% confidence interval, 1.28-8.03), lesion length (hazard ratio, 1.05; 95% confidence interval, 1.02-1.08), residual stenosis (hazard ratio, 1.07; 95% confidence interval, 1.05-1.10), and baseline glucose (hazard ratio, 1.01; 95% confidence interval, 1.00-1.02) were associated with ISR. CONCLUSIONS: Elevated MPV may be associated with ISR after CAS. Patients with high preprocedural MPV may benefit from an intensified antiplatelet therapy after CAS.

Apolipoprotein J as a predictive biomarker for restenosis after carotid endarterectomy: a retrospective study.

Carotid endarterectomy (CEA) is an effective surgical option for stroke prophylaxis in most patients. Restenosis after CEA can lead to re-intervention and adverse events, but the factors predicting restenosis are poorly understood. Apolipoprotein J (ApoJ) is considered to be a novel predictive factor of vascular restenosis and is associated with a large number of processes related to atherosclerosis and cell-cycle phases. The aim of this study was to elucidate the predictive value of Apo J in internal carotid artery (ICA) restenosis following CEA. This retrospective study examined all prospectively collected data for patients who underwent CEA at our surgical department over a 2-year period. The serum ApoJ levels of 100 patients were examined; 56 patients who underwent CEA comprised the vascular group (VG), and 44 patients who underwent minor surgery comprised the control group (CG). ApoJ samples were obtained preoperatively, 24 h after the surgical procedure and at 1, 6 and 12 months thereafter during the follow-up. The preoperative difference in ApoJ levels between the CG and VG was statistically signifcant; the mean values were 39.11±14.16 and 83.03±35.35 µg/mL, respectively. In the VG, the serum ApoJ levels were 112.09±54.40, 71.20±23.70, 69.92±25.76 and 62.25±19.17 µg/mL at postoperative day 1 and at 1, 6 and 12 months post-operatively, respectively, while the ApoJ concentrations of patients in the CG remained unchanged. Further subdivision of the VG into patients with or without restenosis revealed that restenosis patients presented signifcantly higher mean ApoJ values than non-restenosis VG patients. In summary, ApoJ seems to be an important predictor for carotid restenosis at 6 and 12 months postoperatively.

Establishment of prophylactic enoxaparin dosing recommendations to achieve targeted anti-factor Xa concentrations in children with CHD.

BACKGROUND: Enoxaparin may be used to prevent central venous catheter-related thrombosis in patients with CHD. We aimed to determine whether current enoxaparin dosing regimens effectively achieve anti-factor Xa concentrations within prophylactic goal ranges in this patient population. METHODS: We implemented a formal protocol aimed at reducing central venous catheter-related thrombosis in children with CHD in January, 2016. Standard empiric prophylactic enoxaparin dosing regimens were used - for example, 0.75 mg/kg/dose every 12 hours for patients <2 months of age and 0.5 mg/kg/dose every 12 hours for patients ⩾2 months of age - with anti-factor Xa goal range of 0.25-0.49 IU/ml. Patients <2 years of age who received enoxaparin and had at least one valid steady-state anti-factor Xa measurement between 25 January, 2016 and 31 August, 2016 were retrospectively reviewed. RESULTS: During the study period, 47 patients had 186 anti-factor Xa concentrations measured, of which 20 (11%) were above and 112 (60%) were below the prophylactic goal range. Anti-factor Xa concentrations within the goal range were ultimately achieved in 31 patients. Median dose required to achieve anti-factor Xa concentrations within the prophylactic range was 0.89 mg/kg/dose (25, 75%: 0.75, 1.11) for patients <2 months (n=23 patients) and 0.79 mg/kg/dose (25, 75%: 0.62, 1.11) for patients ⩾2 months (n=8 patients). CONCLUSIONS: Enoxaparin doses required to achieve prophylactic anti-factor Xa concentrations in young children with CHD were consistently higher than the currently recommended prophylactic dosing regimens. Further study is needed to determine whether dose titration to achieve prophylactic anti-factor Xa concentrations is effective in preventing central venous catheter-related thrombosis.

Relationship between Serum Albumin Level and Monocyte-to-High-Density Lipoprotein Cholesterol Ratio with Saphenous Vein Graft Disease in Coronary Bypass.

Background Previous studies proposed that inflammation, oxidative stress, and impaired endothelial dysfunction have a crucial role in occurrence of saphenous vein graft (SVG) disease (SVGD). The aim of this study was to assess the relationship between monocyte-to-high-density lipoprotein cholesterol (HDL-C) ratio (MHR) and serum albumin (SA) level as readily available inflammatory and oxidative stress markers with the presence of SVGD in patients with a coronary bypass. Methods In this retrospective cross-sectional study, a total of 257 patients (n = 112 SVGD [+] [mean age was 65.3 ± 8.4 years, 75.0% males] and n = 145 SVGD [-] [mean age was 66.5 ± 10.1 years, 74.5% males]) were enrolled. At least one SVG with ≥ 50% stenosis was defined as SVGD. Independent predictors of SVGD were determined by logistic regression analysis. Results White blood cell, neutrophil, monocyte, the age of SVG, and MHR were significantly higher, whereas SA level was significantly lower in patients with SVGD. In regression analysis, neutrophil, age of SVG, SA (odds ratio [OR]: 0.232 [0.156-0.370], p < 0.001), and MHR (OR: 1.122 [1.072-1.174], p < 0.001) remained as independent predictors of SVGD. Moreover, age of SVG showed a significant negative correlation with SA (r = - 0.343, p < 0.001) and a positive correlation with MHR (r = 0.238, p < 0.001). In the receiver-operating characteristic curve analysis, the cutoff value of ≤ 3.75 g/dL for SA has a 73.2% sensitivity and 64.8% specificity and the cutoff value of ≥ 12.1 for MHR has a 71.4% sensitivity and 60.0% specificity for prediction of SVGD. Conclusion Consequently, to the best of our knowledge, this is the first study showing a significant and independent association between SA and MHR with SVGD.

Add-on Antiplatelet Effects of Eicosapentaenoic Acid With Tailored Dose Setting in Patients on Dual Antiplatelet Therapy.

The aim of this study was to investigate the antiplatelet effects of eicosapentaenoic acid (EPA) at a sufficient dose following coronary stent implantation. Thirty-one patients on dual antiplatelet therapy with aspirin and clopidogrel were treated with highly purified EPA-E (Epadel®) for 12 weeks. Based on our previous study, patients with a high baseline EPA/arachidonic acid (AA) ratio (≥ 0.37; n = 11) were given a standard dose (1800 mg daily) of EPA-E, whereas those with a low EPA/AA ratio (< 0.37; n = 20) were given a high dose (2700 mg daily) to reach the target value of > 0.92. Platelet function was then evaluated with agonist-induced aggregation using light transmittance aggregometry and VerifyNow®. After EPA-E treatment, the EPA/AA ratio significantly increased from 0.28 to 1.31 (P < 0.001). Collagen (1, 2, and 4 µg/mL)-induced maximal platelet aggregation (MPA) was significantly suppressed after EPA-E administration (from 28.0 to 24.0, P = 0.033; from 44.0 to 40.0, P = 0.016; from 60.0 to 56.0, P = 0.010; respectively). However, there were no changes in MPA induced by adenosine diphosphate and AA and in P2Y12 reaction units (PRU) and aspirin reaction units. After EPA-E treatment, PRU was significantly suppressed in 8 patients showing high on-treatment platelet reactivity (HTPR) (baseline 305; 266-321 versus on-treatment 256; 233-261, P = 0.012), but not in those without HTPR (201; 156-220 versus 183; 159-233, P = 0.212). In conclusion, EPA treatment at a sufficient dose suppressed platelet aggregation and showed possible add-on effects in patients with clopidogrel hyporesponsiveness.

Optical Coherence Tomography Assessment of Glucose Fluctuation Impact on the Neointimal Proliferation After Stent Implantation in a Diabetic/Hypercholesterolemic Swine Model.

The aim of the present study was to investigate the effects of glucose fluctuation on neointimal proliferation after stent implantation by optical coherence tomography (OCT) in a diabetic/hypercholesterolemic (DM/HC) swine model.A total of 24 everolimus-eluting stents (EES) were implanted in the right coronary artery (RCA) of the animals using a 20% overstretch ratio. The 24 swines were divided into a DM-high glucose fluctuation (HGF) group (n = 8), DMlow glucose fluctuation (LGF) group (n = 8), and a control group (n = 8). Percent diameter stenosis (%DS), late loss (LL), percent area stenosis (%AS), and neointimal thickness (NIT) were analyzed. The differences in neointimal characteristics and circulating oxidative stress and inflammation biomarkers were assessed and measured.At 28 days, the highest values of %DS, LL, %AS, and NIT were achieved in the HGF group followed by the LGF group (P < 0.05) and the control group (P < 0.05). The highest frequency of the heterogeneous pattern was in the HGF group followed by the LGF group (P < 0.05) and the control group (P < 0.05). This was also the case for the oxidative stress and inflammation biomarkers.DM might have a deleterious impact on neointimal proliferation after EES implantation in this DM/HC swine model. The extent of glucose fluctuation may be related to the degree of neointimal proliferation and this needs to be further confirmed by long-term follow-up and histology.

High platelet reactivity affects the clinical outcomes of patients undergoing percutaneous coronary intervention.

BACKGROUND: The association of platelet reactivity and clinical outcomes, especially stent thrombosis, was not so clear. We sought to investigate whether high platelet reactivity affects clinical outcomes of patients with drug eluting stents (DESs) implantation. METHODS: All enrolled individuals treated with DESs implantation were evaluated by PL-11, using sequentially platelet counting method. The primary end point was the occurrence of definite and probable stent thrombosis at 2 years. The secondary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including all cause death, spontaneous myocardial infarction (MI), target vessel revascularization (TVR), and ischemic stroke. RESULTS: A total of 1331consecutive patients were enrolled at our center. There were 91 patients (6.8 %) identified with high platelet reactivity (HPR) on aspirin, and 437 patients (32.9 %) with HPR on clopidogrel. At 2-year follow-up, the incidence of stent thrombosis was significantly higher in patients with HPR on aspirin (9.9 % vs. 0.4 %, p < 0.001), and HPR on clopidogrel (3.0 % vs. 0.1 %, p < 0.001). There were increased MACCE in the HPR on aspirin group (16.5 % vs. 8.5 %, p = 0.021), mainly driven by the higher all cause death (7.7 % vs. 1.6 %, p = 0.002) and MI (9.9 % vs. 1.9 %, p < 0.001) in the HPR on aspirin group. Similarly, the rate of MACCE was higher in the HPR on clopidogrel group (12.4 % vs. 7.4 %, p = 0.004). No differences in all bleeding and hemorrhagic stroke were observed. CONCLUSIONS: The present study demonstrated that high platelet reactivity on both aspirin and clopidogrel were associated with incremental stent thrombosis following DESs implantation.

Platelet aggregation and risk of stent thrombosis or bleeding in interventionally treated diabetic patients with acute coronary syndrome.

BACKGROUND: Platelet aggregation monitoring in diabetic patients treated with coronary interventions (PCI) for an acute coronary syndrome (ACS) is a promising way of optimizing treatment and outcomes in this high risk group. The aim of the study was to verify whether clopidogrel response measured by Multiplate analyzer (ADPtest) in diabetic ACS patients treated with PCI predicts the risk of stent thrombosis or cardiovascular mortality and bleeding. METHODS: Into this prospective, observational study 206 elective PCI patients were enrolled. Two cutoff points of ADPtest were used in analysis to divide patients into groups. One (345 AU x min) was calculated based on ROC curve analysis; this cutoff provided the best ROC curve fit, although it did not reach statistical significance. The other (468 AU x min) was accepted based on the consensus of the Working Group on On-Treatment Platelet Reactivity. The risk of stent thrombosis and mortality was assessed using Cox regression analysis and Kaplan-Meier curves. RESULTS: The risk of stent thrombosis was higher in the group of patients with impaired clopidogrel response for either cutoff value (for >354 AU x min - HR 12.33; 95% CI 2.49-61.1; P = 0.002). Cardiovascular mortality was also higher in the impaired clopidogrel response group (for >354 AU x min - HR 10.58; 95% CI 2.05-54.58; P = 0.005). We did not find a clear relation of increased clopidogrel response to the risk of bleeding. CONCLUSIONS: The results of this study show that in diabetic ACS patient group treated with PCI an impaired platelet response to clopidogrel measured by the Multiplate analyzer results in increased risk of stent thrombosis and cardiac death.

A potential marker of bare metal stent restenosis: monocyte count - to- HDL cholesterol ratio.

BACKGROUND: Oxidation and inflammation play significant roles in the pathogenesis of coronary artery diseases. Monocyte count to high-density lipoprotein (HDL) cholesterol ratio (MHR) is a new marker and has revealed as an indicator of inflammation in the literature. The present study aimed to search the effect of MHR on in-stent restenosis (ISR) in patients with stable or unstable angina pectoris undergoing bare-metal stent (BMS) implantation. METHODS: A total of 468 consecutive stable or unstable angina pectoris patients (mean age 60.3 ± 10.1 and 70 % men) who had undergone successful BMS implantation were included the study. Serum samples were obtained before the procedure. RESULTS: The mean period between two coronary angiography procedures was 14 ± 7.9 months. The baseline MHR levels were significantly higher in patients that had ISR (odds ratio, 3.64; 95 % confidence interval, 2.45- 4.84; P < 0.001). Stent diameter, the time between the two coronary angiographic studies, uric acid and MHR levels emerged as independent predictors of ISR. CONCLUSIONS: Our results indicate that elevated MHR is an independent and powerful predictor of ISR in patients with stable or unstable angina pectoris who underwent successful BMS implantation.

Pretreatment of synthetic vascular grafts with heparin before implantation, a simple technique to reduce the risk of thrombosis.

Thrombosis of synthetic grafts commonly used in cardiovascular surgery is a major complication. We examined whether pretreatment of the graft with heparin reduces the risk of early thrombosis. A circuit was assembled to compare two pairs of shunts simultaneously in the same animal. The study shunts were pretreated with heparin. After 2 hours of circulation, clot formation was evaluated by image analysis techniques. The pretreated grafts had fewer blood clots adhered to the surface by direct visual inspection. The image analysis showed 5 vs. 39 clots, 0.01% vs. 1.8% clotted area, and 62 vs. 5630 clot pixel area between the treated and non-treated grafts respectively, p < 0.05. Pretreatment of the synthetic graft with heparin prior to implantation reduces the risk of early clot formation. This simple practice might be helpful to prevent initial thrombosis of the graft and later occlusion.

Association of ABO blood types with the risk of in-stent restenosis.

OBJECTIVES: To investigate the prevalence of in-stent restenosis (ISR) in patients with various ABO blood types. METHODS: Clinical information from 150 patients with a confirmed diagnosis of ISR and 150 patients with a diagnosis of patent coronary stents in the secondary angiography was collected. Comprehensive demographic and laboratory data, including ABO and Rhesus blood groups, as well as comorbid conditions and vessel and stent characteristics, were recorded for each patient. The association of ABO blood groups with the risk of ISR before and after controlling for coronary risk factors was determined. Categorical data were analyzed with the Chi-square test and numerical values were analyzed with t-tests. Binary logistic regression models were constructed to compare type A and non-A for the frequency of risk factors. RESULTS: A total of 392 stents were implanted in 300 patients. Two hundred and fourteen stents (54.6%) were patent and 178 stents (45.4%) were stenosed. Blood group A was significantly more common in the ISR group (43.3% vs. 28.7%, p=0.03). However, the frequencies of other blood types, as well as Rh antigen, were similar between the two groups. Triglyceride and low-density lipoproteins were the only significantly different variables (221 ± 198 mg/dL vs. 138 ± 76 mg/dL, p<0.001 and 108 ± 36 mg/dL vs. 96 ± 73 mg/dL, p=0.04, in type-A vs. non-A, respectively). After matching for coronary risk factors, there was no difference between A blood type patients and their controls. CONCLUSION: ISR is significantly more prevalent in individuals with the type A blood group. However, this higher association is most likely due to higher atherogenic conditions in patients within this population.