An association between chronic obstructive pulmonary disease and abdominal aortic aneurysm beyond smoking: results from a case-control study.

OBJECTIVES: It is currently unclear whether the parallels between abdominal aortic aneurysms (AAAs) and chronic obstructive pulmonary disease (COPD) are explained by common risk factors alone, such as cigarette smoking, or by a predetermined cause. Given the persistent controversy with regard to the association between AAA and COPD, we studied this association in depth. METHODS: We conducted a case-control study comparing patients with a small AAA (maximum infrarenal diameter 35-50 mm, n = 221) with controls diagnosed with peripheral artery disease (PAD, n = 87). The controls were matched to the cases for lifetime cigarette smoking. Pulmonary function was measured by spirometry, and all subjects completed a questionnaire on medical history and smoking habits (current, former and never smokers). RESULTS: Aneurysm patients were similar to controls with respect to gender (p = 0.71), lifetime cigarette smoking (39 vs. 34 pack years, p = 0.23) and history of cardiovascular disease (45% vs. 55%, p = 0.12). Aneurysm patients had more airway obstruction (forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) (0.69 ± 0.12 vs. 0.78 ± 0.11, p < 0.001)), which was most pronounced in never smokers (0.73 ± 0.07 vs. 0.86 ± 0.07, p < 0.001). COPD was more prevalent in aneurysm patients (44%; 98/221) than in controls (20%; 17/87) (adjusted odds ratio (OR) 3.0; 95% confidence interval (95%CI) 1.6-5.5, p < 0.001). In particular, a major proportion of AAA patients was newly diagnosed with COPD; only 40 of 98 patients (41%) with COPD (mild, moderate or severe/very severe) were known before with obstructive pulmonary defects and received treatment. CONCLUSIONS: This study confirms an association between AAA and COPD and shows that this association is independent from smoking. Findings also demonstrate that COPD is under-diagnosed in AAA patients.

A comparison of the Doppler-derived maximal systolic acceleration versus the ankle-brachial pressure index or detecting and quantifying peripheral arterial occlusive disease in diabetic patients.

AIM: The aim of this study was to assess the diagnostic accuracy of the Doppler derived maximal systolic acceleration (ACCmax) as a novel technique for evaluating peripheral arterial occlusive disease (PAOD) in patients with diabetes mellitus, who are known for a falsely elevated ankle-brachial index (ABI). METHODS: In this retrospective analysis ACCmax was measured at ankle level in a series of 163 consecutive patients referred to the vascular laboratory for initial assessment of PAOD. Patients were classified according to the presence or absence of diabetes. In the non-diabetic patients PAOD was defined as ABI < or =0.90. This group was used to establish the association between ACCmax and ABI in a linear regression model. The result was then used to predict the presence or absence of PAOD in the diabetic patients. RESULTS: The authors examined 301 lower limbs. The study group consisted of 166 limbs of patients without diabetes and 135 limbs of patients with diabetes. PAOD was present in 52% of limbs in the nondiabetic group versus 59% of limbs in the diabetic group (ABI < or =0.90, or in case of non-compliant vessels toe-brachial index (TBI) < or =0.70). An ACCmax cut-off value of >10 m/s2 was found to be highly predictive for the exclusion of PAOD (negative predictive value 95%). In addition, the ACCmax cut-off value of <6.5 m/s2 was highly predictive for the detection of PAOD (positive predictive value 99%). A strong quadratic association was found between ACCmax and ABI in the non-diabetic group (R2=0.85). In the diabetic patients R2 values were 0.81 and 0.79 after ABI and TBI measurement respectively. CONCLUSION: DUS-derived ACCmax is an accurate marker that could offer significant benefits for the diagnosis of PAOD, especially in diabetic patients.

Vascular growth in ischemic limbs: a review of mechanisms and possible therapeutic stimulation.

Stimulation of vascular growth to treat limb ischemia is promising, and early results obtained from uncontrolled clinical trials using angiogenic agents, e.g., vascular endothelial growth factor, led to high expectations. However, negative results from recent placebo-controlled trials warrant further research. Here, current insights into mechanisms of vascular growth in the adult, in particular the role of angiogenic factors, the immune system, and bone marrow, were reviewed, together with modes of its therapeutic stimulation and results from recent clinical trials. Three concepts of vascular growth have been described to date-angiogenesis, vasculogenesis, and arteriogenesis (collateral artery growth)-which represent different aspects of an integrated process. Stimulation of arteriogenesis seems clinically most relevant and has most recently been attempted using autologous bone marrow transplantation with some beneficial results, although the mechanism of action is not completely understood. Better understanding of the highly complex molecular and cellular mechanisms of vascular growth may yet lead to meaningful clinical applications.

Intramuscular or combined intramuscular/intra-arterial administration of bone marrow mononuclear cells: a clinical trial in patients with advanced limb ischemia.

AIM: Recent evidence indicates that bone marrow mononuclear cells (BMC) promote collateral vessel formation in patients with severe peripheral arterial disease (PAD). However, aspects concerning optimal administration mode, durability and long-term safety require consideration. Combined intra-arterial (IA) plus intramuscular (IM) BMC delivery may be more effective than exclusive intramuscular injections. The aim of this study was to evaluate feasibility, safety and effect of exclusive IM versus combined IM+IA delivery of autologous BMC in patients who were not candidates for surgical or endovascular treatment. METHODS: Twenty-seven patients were treated with either combined IA+IM (N=12) or sole IM (N=15) administration of autologous BMC. Efficacy was assessed after 1, 6 and 12 months. Limb salvage, pain-free walking distance, ankle-brachial pressure index (ABI) and pain scores were evaluated. RESULTS: There were no adverse reactions related to injection of the cells. Three patients died within the first year of follow-up due to non-procedure related causes. Two patients in the IA+IM group required limb amputation because of ongoing critical ischemia versus 7 patients in the IM group (P=0.17). BMC treatment in the remaining patients resulted in a significant and sustained (>12 months) improvement. Pain-free walking distance improved from 81+/-56 meters at baseline to 257+/-126 meters at t=6 months (P=0.0002). Mean ABI increased 23% after 6 months (P=0.01) and pain score reduced for up to 50% as shown by Brief Pain Inventory (P=0.001). CONCLUSION: Both IM and combined IM/IA delivery of autologous BMC are safe, and result in relevant and sustained improvement in a considerable proportion of patients with severe PAD who are not amenable for conventional treatment.

Endovascular brachytherapy for the prevention of restenosis after femoropopliteal angioplasty. Results of the VARA Trial.

AIM: Endovascular brachytherapy (EBT) has been proposed as a method to prevent restenosis. We performed a prospective randomised multicenter study to determine its efficacy for prophylaxis of restenosis after femoropopliteal percutaneous transluminal angioplasty (PTA). METHODS: Patients with symptomatic stenotic or totally occluding lesions in the femoropopliteal artery were randomised to be treated with PTA plus EBT or PTA alone. In case of EBT, 14 Gy was applied by an 192Ir source to the vessel wall. Clinical examination, ankle-brachial pressure index (ABPI) and duplex ultrasound were planned after 6 and 12 months. The primary endpoint was significant restenosis of the treated segment at duplex ultrasound after 12 months. RESULTS: Fifty-three of the 60 patients who eventually met the inclusion criteria could be studied. After 12 months, restenosis rates were 44% (12/27) in the PTA group versus 35% (8/23) in the PTA + EBT group (c2 test, P=0.51). There was no difference in mandatory reintervention between the 2 groups. Overall, EBT resulted in an absolute risk reduction of significant restenosis of 9%, yet in patients with totally occlusive disease this reduction was 32%. CONCLUSIONS: This study suggests an effect of EBT on the occurrence of restenosis only after PTA of occluded femoropopliteal lesions. Due to a too small number of patients analysed this difference is not statistically significant.

Gamma radiation induces positive vascular remodeling after balloon angioplasty: a prospective, randomized intravascular ultrasound scan study.

BACKGROUND: Endovascular brachytherapy (EBT) has been shown to prevent restenosis after percutaneous transluminal coronary angioplasty (PTA) in both animal and clinical studies. However, as yet, the effect of EBT on peripheral arteries is unknown. OBJECTIVE: This intravascular ultrasound scan (IVUS) study evaluates the effect of EBT on the extent of plaque growth and vascular remodeling after PTA of the femoropopliteal artery. METHODS: Twenty-four patients with obstructive disease of the femoropopliteal artery underwent standard PTA. Patients were randomized to receive no additional therapy or additional EBT (192-Iridium) after PTA. IVUS investigation was performed after PTA and at 6-month follow-up. A comparison was made between patients without EBT (n = 16) and with EBT (n = 8) in the change in lumen, vessel, and plaque area and plaque dissections seen with IVUS at 6-month follow-up. RESULTS: At follow-up, IVUS revealed a significant difference in lumen area change between patients without and with EBT (-9% and +23%, respectively; P =.03). This difference was the result of a significant difference in vessel area change (+2% and +19%, respectively; P =.05). In both groups of patients, a similar increase in plaque area (+12% and +16%, respectively; P =.80) was encountered. Plaque dissections encountered immediately after PTA were absent at follow-up in patients without EBT, whereas in four of the eight patients with EBT, a persistent dissection was encountered. CONCLUSION: This randomized IVUS study showed that gamma-radiation after PTA has a positive effect on lumen dimensions at 6-month follow-up by inducing positive vascular remodeling (ie, vascular dilatation); gamma-radiation seemed not to affect plaque growth. In addition, gamma-radiation has an effect on the healing process of dissections after PTA.

Peripheral vascular brachytherapy: an introduction.

The response of cells to ionising radiation has been extensively studied for the past 30 years. When radiation is absorbed in biological material, it can directly ionise a critical site (direct effect) or interact with other molecules to produce reactive free radicals, which can subsequently damage critical biological molecules (indirect effect). DNA is considered the critical target damaged by ionising radiation by both direct and indirect processes. Since radiotherapy had proven to be effective in the treatment of non-malignant proliferative processes, it was assumed that this adjunctive treatment would also inhibit vascular restenosis. The major difference between external and intravascular radiation is dose distribution. Intravascular delivery results in extremely high doses to the lumen with a fall-off in dose as a function of distance from the source; whereas, external beam would deliver a uniform dose over the entire volume of tissue treated. Unlike in the coronary circulation most of the peripheral vessels treated are greater than 3 mm in diameter; in fact many are 7 to 10 mm in diameter. Since beta radiation is related to lower penetration properties and more heterogeneous distribution of radiation in comparison to gamma radiation, it is therefore necessary to use a gamma radiation source because it would be difficult to irradiate the sub-intimal tissue with a beta source centred in a large vessel. Radiation can and does have the potential to destroy blood vessels. The challenge in vascular brachytherapy is to treat blood vessels to a point where restenosis is inhibited; yet the vessel is not irreparably damaged.

Resection of the paraesophageal hernia sac.

A simple technique for resection and closure of the paraesophageal hernia sac is described.