Kunihiro Shigematsu

Family history of aortic aneurysm is an independent risk factor for more rapid growth of small abdominal aortic aneurysms in Japan

OBJECTIVE We aimed to investigate risk factors associated with more rapid growth of abdominal aortic aneurysms (AAA) <50 mm (small AAAs) in Japan. METHODS We retrospectively investigated the clinical data of 374 patients with small AAAs (maximum diameter, ≤50 mm) who were referred to The University of Tokyo Hospital, Tokyo Medical University Hospital, or Saitama Medical Center, between 1995 and 2008. RESULTS A total of 374 patients (321 men and 53 women) were followed up for a median of 66 months. The median diameter on initial examination was 40 mm, and the median growth rate of the AAAs was 2.1 mm/y. The growth rate of AAAs with an initial diameter ≥45 mm was significantly greater than those with an initial diameter <45 mm (3.3 mm/y vs 2.0 mm/y, respectively; P = .007). The growth rate of AAAs was significantly greater in patients with hypertension than in those without (2.3 mm/y vs 1.7 mm/y, respectively; P = .006) and in patients with a family history of aortic aneurysm than in those without (4.2 mm/y vs 2.0 mm/y, respectively; P = .009). Logistic regression analysis revealed that a large initial diameter and family history of aortic aneurysm were independent predictors of accelerated growth rate of small AAAs in Japan. CONCLUSIONS In the present study, a large initial diameter and family history of aortic aneurysm were independent risk factors for more rapid growth of small AAAs. Although few studies have reported similar findings thus far, family history of aortic aneurysm should be carefully considered during follow-up of patients with small AAAs.

Efficacy of Revascularization for Critical Limb Ischemia in Patients with End-stage Renal Disease

OBJECTIVE To evaluate the outcomes of surgical revascularization for critical limb ischemia in patients with end-stage renal disease (ESRD). PATIENTS AND METHODS From 2004 to 2010, 184 patients with 213 critically ischaemic limbs caused by arteriosclerosis were admitted to The University of Tokyo Hospital. The outcomes of primarily surgical revascularization-based treatments were retrospectively compared in patients with ESRD (ESRD group: 79 patients, 101 limbs) and without ESRD (non-ESRD group: 105 patients, 112 limbs) during the same period. RESULTS Arterial reconstruction was performed on 56 limbs in 46 patients in the ESRD group and 78 limbs in 73 patients in the non-ESRD group (55% vs. 70%; p = .03). Major amputation was performed in 6 of 48 limbs with patent grafts in the ESRD group because of uncontrolled infection or progression of necrosis. The limb salvage rate after arterial reconstruction was significantly lower in the ESRD group than in the non-ESRD group (p = .0019). The postoperative survival rate was lower in the ESRD group than in the non-ESRD group, although this difference was not significant (p = .052). Associated cardiovascular disease and systemic infection were the most frequent causes of death in the ESRD group. There was no significant difference in graft patency between the two groups after distal bypass surgery; however, the limb salvage rate was significantly lower in the ESRD group than in the non-ESRD group (p = .03). CONCLUSIONS Critical limb ischemia associated with ESRD has a poor prognosis. Infection control is particularly important for achievement of good treatment outcomes.

Surgical result of critical limb ischemia due to tibial arterial occlusion in patients with systemic scleroderma

OBJECTIVE To analyze the outcome after surgery for critical limb ischemia (CLI) due to tibial artery occlusion in patients with systemic scleroderma. METHODS The medical records of scleroderma patients with CLI due to tibial artery occlusion were reviewed with respect to demographic data and perioperative variables. RESULTS Eight patients were identified at The University of Tokyo Hospital from 1991 to 2007. The underlying collagen disease was progressive systemic scleroderma in 6 patients and CREST syndrome in 2 patients. The subjects were 1 man and 7 women with a mean age of 68 years. While hypercoagulability including positive anticardiolipin antibodies was found in only 1 patient, all patients were antinuclear antibody (ANA) positive and 6 of 8 patients had a high titer of centromere-type ANA. Five underwent pedal artery bypass and 1 underwent distal peroneal artery bypass, while 2 underwent primary limb amputation. Although 1 patient with bypass had early graft occlusion (with subsequent below-knee amputation), the other 5 patients with patent grafts quickly achieved pain relief and initial wound healing. However, four of the five patent grafts developed graft occlusion several months after surgery, with severe intimal thickening at the anastomosis. As a result, 2 of 6 patients with bypass (totally 4 of 8 patients) underwent limb loss and 1 patient developed persistent recurrent ulcer. CONCLUSION Bypass surgery in patients with scleroderma and CLI can be successful in achieving early pain relief and ischemic wound healing. However, the long-term effectiveness is limited with high rates of graft failure and limb loss.

Genome-Wide Association Study of Peripheral Arterial Disease in a Japanese Population.

Characteristics of peripheral arterial disease (PAD) are the occlusion or stenosis of multiple vessel sites caused mainly by atherosclerosis and chronic lower limb ischemia. To identify PAD susceptible loci, we conducted a genome-wide association study (GWAS) with 785 cases and 3,383 controls in a Japanese population using 431,666 single nucleotide polymorphisms (SNP). After staged analyses including a total of 3,164 cases and 20,134 controls, we identified 3 novel PAD susceptibility loci at IPO5/RAP2A, EDNRA and HDAC9 with genome wide significance (combined P = 6.8 x 10−14, 5.3 x 10−9 and 8.8 x 10−8, respectively). Fine-mapping at the IPO5/RAP2A locus revealed that rs9584669 conferred risk of PAD. Luciferase assay showed that the risk allele at this locus reduced expression levels of IPO5. To our knowledge, these are the first genetic risk factors for PAD.

Long-term outcomes of surgical treatment in patients with popliteal artery entrapment syndrome.

The object of the study is to determine the long-term outcomes of surgical treatment of patients with popliteal artery entrapment syndrome at a single institute. We retrospectively reviewed 19 limbs of 16 consecutive patients who underwent surgery for popliteal artery entrapment syndrome at our hospital over the past 36 years. The popliteal artery was stenotic in 11 limbs, occlusive in 7 limbs, and compressed and deviated by the medial head of the gastrocnemius muscle but not damaged in 1 limb. Six limbs were treated with autologous saphenous vein bypass, 10 with bypass or venous patch graft concomitant with musculotendinous section, and 3 limbs underwent musculotendinous section alone. The 10-year cumulative patency of the 13 limbs treated with bypass was 100%, although two of them showed occlusion at 23 and 12 years after surgery. One patient who received a venous patch graft showed occlusion 15 years after surgery. Additionally, one asymptomatic patient with an apparently non-damaged popliteal artery who received preventive musculotendinous section alone showed stenosis of the artery 2 years after musculotendinous section. In conclusion, the bypass patency observed in this study was excellent in the long term. Careful examination of popliteal artery anatomy using imaging studies is essential for selecting the appropriate surgical procedure for popliteal artery entrapment syndrome.

Favorable outcomes of very elderly patients with critical limb ischemia who undergo distal bypass surgery

OBJECTIVE To determine the midterm outcomes of distal bypass surgery for very elderly patients, and to determine the ideal candidates for this procedure. METHODS Of 268 consecutive patients (328 limbs) with critical limb ischemia who were treated between 2006 and 2013, 106 (126 limbs) underwent distal bypass and were retrospectively reviewed. Nineteen patients (22 limbs) were aged ≥80 years (very elderly group) and 87 patients (104 limbs) were aged <80 years (control group). RESULTS The baseline characteristics differed between the 2 groups in terms of regular hemodialysis rate (very elderly group, 4 [21%] vs control group, 60 [69%]; P = .0002) and the Charlson comorbidity index (very elderly group, 3.2 ± 1.7 vs control group, 5.0 ± 2.0; P = .0005). According to the Rutherford category of limb ischemia (4/5/6), the very elderly and control groups were classified as 5/17/0 and 11/87/6, respectively (P = .18). Before the surgery, 17 patients (77%) and 67 patients (64%) were ambulatory in the very elderly and control groups, respectively. At follow-up at 29 ± 22 months, the rates of primary (P = .33) and secondary patency (P = .14), limb salvage (P = .50), survival (P = .26), amputation-free survival (P = .42), major adverse limb event and also perioperative death (P = .11), and major adverse cardiovascular events (P = .36) did not significantly differ between the groups. In multivariate analysis, a history of coronary artery disease (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.3-5.9; P = .005), preoperative nonambulatory status (HR, 4.2; 95% CI, 2.1-8.1; P < .0001), and serum albumin levels <3 g/dL (HR, 2.7; 95% CI, 1.3-5.4; P = .01) were significantly related to poor amputation-free survival. Thirteen patients (59%) remained ambulatory at the latest follow-up. In 91 patients (110 limbs) with tissue loss, the Society for Vascular Surgery lower extremity threatened limb classification system: risk stratification based on Wound, Ischemia, and foot Infection classification stages 3 and 4 negatively affected complete wound healing, according to multivariate analysis (HR, 0.34; 95% CI, 0.20-0.61; P = .0005). CONCLUSIONS A very elderly age should not preclude a patient from undergoing distal bypass surgery. A history of coronary artery disease, a nonambulatory status, and hypoalbuminemia, along with the Wound, Ischemia, and foot Infection classification for patients with tissue loss, should be carefully considered to obtain the most benefit from distal bypass surgery.

Viscoelastic Deterioration of the Carotid Artery Vascular Wall is a Possible Predictor of Coronary Artery Disease

AIM The viscoelastic properties of the artery are known to be altered in patients with vascular diseases. However, few studies have evaluated the viscoelasticity of the vascular wall in humans. We sought to investigate the degree of viscoelastic deterioration of the carotid artery and assess its clinical implications. METHODS Between January 2011 and June 2013, patients in whom the toe-brachial index was measured at the vascular laboratory were included in this single-institute retrospective observational study. I(＊), a parameter of viscoelastic deterioration, was computed using a non-invasive ultrasonic Doppler effect sensor on the carotid artery. I(＊) is a non-dimensional value, and I(＊)>0 is considered abnormal. Other patient characteristics were identified and tested for correlations with I(＊). RESULTS The study included 383 patients. The mean I(＊) value was 0.13 ± 0.22 with a normal distribution. Factors that increased the I(＊) value were a female sex (0.18 ± 0.23 vs. 0.10 ± 0.21, P<0.001), age ≥ 60 (0.14 ± 0.22 vs. 0.06 ± 0.23, P<0.05) and systolic blood pressure of >140 (0.15 ± 0.22 vs. 0.10 ± 0.22, P<0.05). I(＊) abnormality was a significant risk factor for coronary artery disease (OR 2.20, 95% CI 1.00-4.80, P<0.05) in a univariate analysis. In the multivariate analysis, I(＊) abnormality was also found to be an independent risk factor for coronary artery disease (OR 4.56, 95% CI 1.21-30.1, P<0.05). CONCLUSIONS I(＊) may reflect the degree of atherosclerotic changes in the arterial wall and could possibly be used to predict coronary artery disease.

Bowel necrosis following endovascular revascularization for chronic mesenteric ischemia: a case report and review of the literature

BackgroundEndovascular revascularization has recently been established as a less invasive treatment method for chronic mesenteric ischemia. However, intestinal necrosis caused by distal embolization following this procedure has not been emphasized.Case presentationThe present report describes a 59-year-old man who was treated with endovascular revascularization for chronic mesenteric ischemia. After the procedure, he was diagnosed with intestinal necrosis caused by distal embolization. Despite emergent bowel resection, he died on postoperative day 109.ConclusionAlthough endovascular revascularization for chronic mesenteric ischemia is less invasive and may be suitable for high-risk patients, attention should be paid to avoid embolic complications that can cause intestinal infarction possibly leading to a fatal condition.

Study Design of PROCEDURE Study. A Randomized Comparison of the Dose-Dependent Effects of Pitavastatin in Patients with Abdominal Aortic Aneurysm with Massive Aortic Atheroma: Prevention of Cholesterol Embolization during Endovascular and Open Aneurysm Repair with Pitavastatin (PROCEDURE) Study.

Outcomes of abdominal aortic aneurysm (AAA) repair have improved in the 2 decades since the emergence of endovascular aneurysm repair (EVAR). However, EVAR is considered a contraindication for shaggy aorta because of the high risk of shower embolization. Recently, statins have been implicated in preventing embolization in patients with shaggy aorta via its pleiotropic effects, including atheroma reduction and coronary artery stabilization. We selected pitavastatin, a statin with potent effects, discovered and developed by a Japanese company because it has shown excellent pleiotropic effects on atheromatous arteries in the Japanese population. A randomized comparison study of dose-dependent effects of pitavastatin in patients with AAA with massive atheromatous aortic thrombus (PROCEDURE study) has begun. PROCEDURE has an enrollment goal of up to 80 patients with AAA with massive aortic atheroma (excluding intrasac atheroma), randomly allocated into 2 groups receiving pitavastatin at a dose of 1 or 4 mg/day. The endpoints of the PROCEDURE study include change in atheroma volume, major adverse events related to shower embolization after aneurysm repair, and lipid-lowering effects. When complete, results of the PROCEDURE study should provide objective evidence to use statins preoperatively for AAA with massive aortic atheroma.

Anti-angiogenic drug AGM1470 suppresses smooth muscle cell migration induced by endothelial PDGF.

OBJECTIVES To examine the effects of the anti-angiogenic drug AGM1470 on smooth muscle cell (SMC) migration activity stimulated by endothelial cell (EC)-derived mitogen. MATERIALS AND METHODS Study 1; ECs were cultured under pulsatile flow using MCDB151 medium. From the supernatant of these EC dishes we devised two types of conditioned medium; anti-PDGF(+) containing 10 micrograms/ml anti-PDGF antibody, and anti-PDGF(-) containing no antibody. SMCs were cultured using both media. Study 2; ECs were cultured under the same conditions using both types of medium; MCDB151 medium containing 10 ng/ml AGM1470, and MCDB151 medium alone. After the AGM1470 concentration had been adjusted to 10 ng/ml, SMCs were cultured using each medium; AGM-exposed EC and AGM-non-exposed EC. SMC colony spreading distances were measured as an index of mitogenic activity for 4 days. RESULTS Study 1; the anti-PDGF(-) group showed an apparently greater spreading distance than the anti-PDGF(+) group. Study 2; the AGM-non-exposed EC group showed a significantly greater spreading distance than the AGM-exposed EC group. However, MTT assay revealed no differences in proliferation between the two groups. CONCLUSION AGM1470 suppresses the EC production of this PDGF-like mitogen as well as SMC migration activity.