Mitsuyoshi Takahara

Angiographic Restenosis and Its Clinical Impact after Infrapopliteal Angioplasty

OBJECTIVE To assess 3- and 12-month angiographic restenosis rates and their clinical impact after infrapopliteal angioplasty. DESIGN Prospective multicenter study. MATERIALS AND METHODS We analyzed 68 critical ischemic limbs (tissue loss: 58 limbs) from 63 consecutive patients due to isolated infrapopliteal lesions who underwent angioplasty alone. Primary endpoint was 3-month angiographic restenosis rate; secondary endpoints were 12-month angiographic restenosis rate, and 3- and 12-month rates of mortality, major amputation and reintervention. Three- and 12-month frequency of ambulatory status and of freedom from ischemic symptoms, and time to wound healing in the ischemic wound group, were compared between restenotic and non-restenotic groups. Angiographic restenosis predictors were assessed by multivariable analysis. RESULTS 95% of cases had 3-month angiography; restenosis rate was 73%: 40% restenosis and 33% re-occlusion. Twelve-month follow-up angiography was conducted for the patients without 3-month angiographic restenosis, and restenosis rate at 12 months was 82%. Non-administration of cilostazol and statin, and chronic total occlusion were 3-month angiographic restenosis predictors. Three- and 12-month mortality was 5% and 12%, respectively. Despite no patients having undergone amputation, 15% had persistent ischemic symptoms, and 48% of limbs underwent reintervention within 12 months. During the same study period, ambulatory status and limbs with complete healing were more frequently observed in the non-restenosis group than in the restenosis group. In the tissue loss group, time to wound healing in the restenosis group was longer than in the non-restenosis group (127 days vs. 66 days, p = 0.02). CONCLUSION The extremely high angiographic restenosis rate after infrapopliteal angioplasty may adversely impact clinical status improvement.

Circulating soluble RAGE as a predictive biomarker of cardiovascular event risk in patients with type 2 diabetes.

It is still controversial whether circulating soluble form of receptor for AGE (sRAGE) is associated with atherosclerosis in diabetic patients. In this study, we enrolled 276 Japanese type 2 diabetic subjects without history of cardiovascular disease (CVD), assessed their baseline clinical and biochemical data including serum sRAGE levels, and prospectively evaluated the association between these parameters and CVD events. The median follow-up period was 5.6 years and there were 25 new CVD events. The tertile analysis showed that the risk for CVD events was higher as serum sRAGE levels were increased (p for trend = 0.046). A multivariate Cox proportional hazards regression analysis revealed that serum sRAGE levels were independently associated with CVD (HR per 1SD = 1.59, 95% CI 1.04-2.45, p = 0.034), even after adjusting for conventional coronary risk factors. In summary, elevated sRAGE levels were associated with the increased risk of CVD in Japanese type 2 diabetic subjects.

Serum vitamin D levels are decreased and associated with thyroid volume in female patients with newly onset Graves' disease.

It has been shown that vitamin D deficiency is associated with autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), multiple sclerosis (MS) and type 1 diabetes (T1DM), and that vitamin D supplementation prevents the onset and/or development of these autoimmune diseases [1]. Furthermore, it was reported more recently that patients with Hashimoto’s thyroiditis, an autoimmune thyroid disease had lower vitamin D levels [2]. However, there are few studies examining vitamin D status in patients with newly onset Graves’ disease. In the present study, we evaluated the vitamin D status in female patients with newly onset GD and the association of serum vitamin D levels with the clinical factors related to GD.

1-Year Results of the ZEPHYR Registry (Zilver PTX for the Femoral Artery and Proximal Popliteal Artery): Predictors of Restenosis.

OBJECTIVES This study sought to assess the rate and predictors of 1-year restenosis after drug-eluting stent implantation for femoropopliteal (FP) lesions in patients with peripheral arterial disease. BACKGROUND Zilver PTX, a paclitaxel-eluting stent for FP lesions, provides superior outcomes to angioplasty and bare-metal stents in clinical trials. However, its real-world outcomes and the associated features remain unclear. METHODS This was a prospective multicenter study enrolling 831 FP lesions (797 limbs, 690 patients) treated by Zilver PTX implantation. The primary endpoint was 1-year restenosis. Secondary endpoints included major adverse limb event and stent thrombosis. RESULTS Mean lesion length was 17 ± 10 cm. One-year restenosis, major adverse limb event, and stent thrombosis rates were 37%, 22%, and 2%, respectively. The generalized linear mixed model showed that lesion length ≥16 cm assessed by angiography and distal external elastic membrane area ≤27 mm(2) and minimum stent area ≤12 mm(2) assessed by intravascular ultrasound were independent risk factors for restenosis. One-year restenosis rates were 15% in cases with none of these risk factors and 50% in those with ≥2 risk factors. CONCLUSIONS The current study demonstrated 1-year real-world outcomes after drug-eluting stent treatment for FP lesions, including challenging ones in clinical practice. Lesion length, external elastic membrane area, and minimum stent area were independent predictors for restenosis. (Zilver PTX for the Femoral Artery and Proximal Popliteal Artery-Prospective Multicenter Registry [ZEPHYR]; UMIN000008433).

Clinical efficacy of endovascular therapy for patients with critical limb ischemia attributable to pure isolated infrapopliteal lesions

BACKGROUND Prognosis of endovascular therapy (EVT) for isolated infrapopliteal lesions has not been adequately studied. We investigated and risk-stratified long-term prognosis after EVT for critical limb ischemia (CLI) attributable to isolated infrapopliteal lesions. METHODS Between March 2004 and October 2010, 884 patients (1057 limbs) with CLI attributable to isolated infrapopliteal lesions who underwent EVT with angioplasty alone were enrolled. Outcome measures were freedom from major adverse limb events with perioperative death (MALE+POD) and amputation-free survival. Cox proportional hazards models were used to assess independent predictors for these outcomes. RESULTS Freedom from MALE+POD was 82 ± 1% and 74 ± 2% at 1 and 5 years, respectively. Risk factors associated with MALE+POD were age ≥80 years (adjusted hazard ratio [HR], 0.4; P < .001), nonambulatory status (HR, 2.0; P < .001), albumin <3.0 g/dL (HR, 1.4; P < .0001), Rutherford 6 (HR, 2.2; P < .001), C-reactive protein ≥3.0 mg/dL (HR, 2.1; P < .001), and below-the-ankle disease (HR, 2.0; P < .001). One- and 5-year amputation-free survival was 71 ± 2% and 38 ± 3%, respectively. Risk factors associated with major amputation/mortality were nonambulatory status (adjusted HR, 2.1; P < .001), body mass index <18.5 kg/m(2) (HR, 1.4; P = .02), albumin <3.0 g/dL (HR, 1.8; P < .0001), end-stage renal disease (HR, 1.4; P = .004), ejection fraction <50% (HR, 1.6; P < .001), Rutherford 6 (HR, 1.9; P < .001), C-reactive protein ≥3.0 mg/dL (HR, 1.7; P < .0001), and below-the-ankle disease (HR, 1.8; P < .001). In patients with more than four risk factors, both end points at 1 year were below the 71% suggested efficacy objective performance goal. CONCLUSIONS Long-term clinical outcomes were acceptable after EVT for patients with CLI due to pure isolated infrapopliteal lesion. Risk stratification by baseline characteristics is useful in estimating long-term prognosis.

The Influence of Glycemic Control on the Prognosis of Japanese Patients Undergoing Percutaneous Transluminal Angioplasty for Critical Limb Ischemia

OBJECTIVE To reveal the influence of preoperative factors on the prognosis of patients undergoing percutaneous transluminal angioplasty (PTA) for critical limb ischemia (CLI). RESEACH DESIGN AND METHODS We recruited 278 Japanese patients who underwent PTA for CLI between 2003 and 2009. The outcome measures were mortality and major amputation. Cox proportional hazards regression analyses were performed. RESULTS The prevalence of diabetes was 71%, and A1C was 7.0 ± 1.4%. The follow-up period was 90 ± 72 weeks, and 48 patients underwent major amputations and 89 died. The presence of diabetes in the whole population and A1C level in the diabetic population had no influence on morality; rather, mortality was associated with age (P = 0.007), impaired activities of daily living (P < 0.001), hemodialysis (P < 0.001), and albumin level (P = 0.010). In contrast, the presence of diabetes and A1C level had significant association with major amputation (P = 0.012 and P = 0.007, respectively). The quartile analysis showed that diabetic subjects with an A1C ≥6.8%, but not <6.8%, had a significantly higher risk of major amputation than nondiabetic subjects. The adjusted hazard ratio of diabetes with A1C ≥6.8% was 2.907 (95% CI 1.606–5.264) (P < 0.001). CONCLUSIONS Diabetes with poor glycemic control is associated with major amputation, but not mortality, in CLI patients undergoing PTA. Prognostic indicators seem somewhat different between survival and limb salvage in the population.

Serum vitamin D levels are decreased in patients without remission of Graves’ disease

Graves’ disease (GD) is an autoimmune thyroid disease in which thyrotropin receptor autoantibodies (TRAb) cause hyperthyroidism. Although medical treatment with antithyroid drugs (ATD) is the first choice treatment for GD in Japan and Europe, a remission rate of GD with ATD is not satisfactory, and many patients need long-term treatment with ATD or further treatments such as radioactive iodine therapy or thyroidectomy [1]. Therefore, it is very important to identify the factors relating to the remission of GD. It has been recently shown that vitamin D deficiency is associated with the onset and/or development of several autoimmune diseases, including multiple sclerosis (MS), inflammatory bowel disease (IBD), and type 1 diabetes (T1DM) [2]. Furthermore, it has been reported more recently that patients with autoimmune thyroid diseases including GD have lower vitamin D status [3, 4]. However, there is no study comparing vitamin D status between the patients with and without remission of GD. In the present study, we examined vitamin D status in female patients with and without remission of GD and discussed the role of vitamin D in the pathogenesis and/or prognosis of GD.

Basal Insulin Requirement Is ∼30% of the Total Daily Insulin Dose in Type 1 Diabetic Patients Who Use the Insulin Pump

OBJECTIVE To investigate the basal insulin requirement in total daily insulin dose in Japanese type 1 diabetic patients who use the insulin pump. RESEARCH DESIGN AND METHODS The basal insulin requirement in 35 type 1 diabetic patients without detectable C-peptide using the insulin pump (Paradigm 712) was investigated during 2–3 weeks of hospitalization. The patients were served diabetic diets of 25–30 kcal/kg ideal body weight. Each meal omission was done to confirm stable blood glucose levels within 30 mg/dL variance until the next meal. Target blood glucose level was set at 100 mg/dL before each meal and 150 mg/dL at 2 h after each meal. RESULTS Total daily insulin dose was 31.6 ± 8.5 units, and total basal insulin requirement was 8.7 ± 2.9 units, which was 27.7 ± 6.9% of the total daily dose. CONCLUSIONS Basal insulin requirement is ∼30% of the total daily dose in Japanese type 1 diabetic patients who use the insulin pump.

3-Year Outcomes of the OLIVE Registry, a Prospective Multicenter Study of Patients With Critical Limb Ischemia: A Prospective, Multi-Center, Three-Year Follow-Up Study on Endovascular Treatment for Infra-Inguinal Vessel in Patients With Critical Limb Ischemia.

OBJECTIVES This study sought to investigate the 3-year follow-up results of OLIVE registry patients. BACKGROUND Although favorable 12-month clinical outcomes after endovascular therapy (EVT) in OLIVE registry patients with critical limb ischemia (CLI) from infrainguinal disease have been reported, long-term results after EVT remain unknown. METHODS This was a prospective multicenter registry study that consecutively enrolled patients who received infrainguinal EVT for CLI. The primary outcome was 3-year amputation-free survival (AFS), whereas secondary outcome measures were 3-year freedom from major adverse limb events (MALE), wound-free survival, and wound recurrence rate. Prognostic predictors for each outcome were also elucidated by Cox proportional hazard regression analysis or the log-rank test. RESULTS The completion rate of 3-year follow-up was 95%. Three-year AFS, freedom from MALE, and wound-free survival rates were 55.2%, 84.0%, and 49.6%, respectively. Wound recurrence out to 3 years was 43.9%. After multivariable analysis, age (hazard ratio [HR]: 1.43, p = 0.001), body mass index ≤18.5 (HR: 2.17, p = 0.001), dialysis (HR: 2.91, p < 0.001), and Rutherford 6 (HR: 1.64, p = 0.047) were identified as predictors of 3-year major amputation or death. Statin use (HR: 0.28, p = 0.02), Rutherford 6 (HR: 2.40, p = 0.02), straight-line flow to the foot (HR: 0.27, p = 0.001), and heart failure (HR: 1.96, p = 0.04) were identified as 3-year MALE predictors. Finally, CLI due to isolated below-the-knee lesion was a wound recurrence predictor (HR: 4.28, p ≤ 0.001). Three-year survival, freedom from major amputation, and reintervention rates were 63.0%, 87.9%, and 43.2%. CONCLUSIONS In CLI patients with infrainguinal lesions, 3-year clinical results of EVT were reasonable despite high reintervention and moderate ulcer recurrence rate. (A Prospective, Multi-Center, Three-Year Follow-Up Study on Endovascular Treatment for Infra-Inguinal Vessel in Patients With Critical Limb Ischemia [OLIVE 3-Year Follow-Up Study]; UMIN000014759).

Predictive scoring model of mortality after surgical or endovascular revascularization in patients with critical limb ischemia

OBJECTIVE The latest guideline points to life expectancy of <2 years as the main determinant in revascularization modality selection (bypass surgery [BSX] or endovascular therapy [EVT]) in patients with critical limb ischemia (CLI). This study examined predictors and a predictive scoring model of 2-year mortality after revascularization. METHODS We performed Cox proportional hazards regression analysis of data in a retrospective database, the Bypass and Endovascular therapy Against Critical limb ischemia from Hyogo (BEACH) registry, of 459 consecutive CLI patients who underwent revascularization (396 EVT and 63 BSX cases between January 2007 and December 2011) to determine predictors of 2-year mortality. The predictive performance of the score was assessed with the area under the time-dependent receiver operating characteristic curve. RESULTS Of 459 CLI patients (mean age, 72 ± 10 years; 64% male; 49% nonambulatory status, 68% diabetes mellitus, 47% on regular dialysis, and 18% rest pain and 82% tissue loss as treatment indication), 84 died within 2 years after revascularization. In a multivariate model, age >75 years (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.10-2.85), nonambulatory status (HR, 5.32; 95% CI, 2.96-9.56), regular dialysis (HR, 1.90; 95% CI, 1.10-3.26), and ejection fraction <50% (HR, 2.49; 95% CI, 1.48-4.20) were independent predictors of 2-year mortality. The area under the time-dependent receiver operating characteristic curve for the developed predictive BEACH score was 0.81 (95% CI, 0.76-0.86). CONCLUSIONS Predictors of 2-year mortality after EVT or BSX in CLI patients included age >75 years, nonambulatory status, regular dialysis, and ejection fraction <50%. The BEACH score derived from these predictors allows risk stratification of CLI patients undergoing revascularization.