Association between the coronary artery disease risk locus on chromosome 9p21.3 and abdominal aortic aneurysm.

BACKGROUND: Recent genome-wide studies have shown a significant association of a locus on chromosome 9p21.3 and coronary artery disease. We performed a case-control study to investigate the association between this locus and abdominal aortic aneurysm (AAA). METHODS AND RESULTS: A total of 1714 patients (899 patients with AAA and 815 controls) were genotyped for the lead single-nucleotide polymorphism, rs1333049, on chromosome 9p21. The frequency of the C (risk) allele of rs1333049 in the control group was 0.471. There was a significant association between the C allele and AAA (odds ratio, 1.22; 95% confidence interval, 1.06 to 1.39; P=0.004). The genotypic-specific odds ratios (compared with the GG genotype) were 1.17 (95% confidence interval, 0.93 to 1.47; P=0.191) for the GC genotype and 1.50 (95% confidence interval, 1.14 to 1.97; P=0.004) for the CC genotype. In logistic regression modeling, the association of the CC genotype with AAA was independent of the presence of clinical coronary artery disease (odds ratio, 1.46; 95% confidence interval, 1.11 to 1.94; P=0.008). CONCLUSIONS: Our study shows that the recently identified chromosome 9 variant that increases risk of coronary artery disease is also associated with the presence of AAA. The findings suggest that the effect of this locus on risk of cardiovascular disease extends beyond the coronary circulation.

The interleukin-10-1082 'A' allele and abdominal aortic aneurysms.

BACKGROUND: Abdominal aortic aneurysms (AAA) are caused by inflammatory processes in the wall of the aorta resulting in degradation of structural proteins. This inflammatory process is mediated, in part, by cytokines, and interleukin-10 (IL-10) is a predominantly anti-inflammatory cytokine. A single nucleotide polymorphism in the promoter region of the IL-10 gene that affects transcription has been associated with AAA in a small study. The aim of this study was to determine whether this polymorphism is associated with AAA and also examine its effect on the growth of small AAA. METHODS AND RESULTS: A case control study was performed. A total of 389 patients with AAA and 404 healthy controls were recruited. IL-10-1082 polymorphisms were determined by polymerase chain reaction-based methods. In the case of patients with small AAA (<5.5 cm), serial size measurements were recorded to determine mean growth rate. There was a statistically significant difference both in allele and genotype frequencies between the case and control groups with the IL-10-1082 'A' allele being more common in the AAA group (P = .006). In the AAA group, genotype frequencies were as follows: GG 84, GA 201, and AA 104. In the control group, the genotype frequencies were GG 118, GA 205, and AA 81. The odds ratio for the 'A' allele as a risk factor for AAA was 1.50 (95% confidence interval 1.09 to 2.07). Regression modeling revealed that the IL-10-1082 genotype was, however, not independently associated with AAA if age, tobacco use, hypertension, and history of coronary or peripheral artery disease was taken into account. There was a trend towards lower plasma IL-10 level in IL-10 AA carriers, but the IL-10 'A' allele did not have any discernible effect on the growth of small AAA. CONCLUSIONS: This study demonstrates that the IL-10-1082 'A' allele is associated with AAA, although this association is likely to be secondary to an association between IL-10-1082 genotype and other markers of cardiovascular disease rather than AAA per se.

The value of urgent carotid surgery for crescendo transient ischemic attacks.

OBJECTIVE: This study audited operative risk in patients undergoing urgent carotid surgery for crescendo transient ischemic attacks (TIAs). METHODS: Interrogation of the vascular unit database (January 1992 to July 2004) identified 42 patients operated on urgently for crescendo TIAs, which were defined as>or=3 TIAs within the preceding 7 days. Stroke, death, and any major cardiac events were analyzed. RESULTS: Thirty-nine patients underwent conventional endarterectomy, and three underwent interposition vein bypass. Crescendo TIA patients had sustained a median of five TIAs (range, 3 to 20) in the 7 days before surgery. Three patients died or had a stroke after surgery, for a combined stroke/death rate of 7%. This compares with 2.4% in 1000 patients undergoing elective carotid endarterectomy in this unit during the same time period. The combined stroke/death/major cardiac event rate was 14% (n=6). CONCLUSIONS: The combined risk of neurologic and cardiac complications after urgent carotid surgery for crescendo TIA is higher than that expected after elective cases but is still acceptable considering the natural history of patients with unstable neurologic symptoms.

Subintimal recanalization of the femoropopliteal segment to promote healing of an ulcerated below-knee amputation stump.

PURPOSE: To describe the use of the subintimal technique to revascularize an ulcerated below-knee amputation stump. CASE REPORT: A 64-year-old man with persistent ulceration of a below-knee amputation stump underwent attempted percutaneous revascularization. Via antegrade puncture, the femoropopliteal occlusion was recanalized subintimally and eventually opened into a large medial geniculate collateral branch, improving the stump flow. The procedure was uneventful, and at 6 months, the patient was pain-free and able to mobilize with his prosthetic limb. CONCLUSION: Subintimal revascularization of a critically-ischemic below-knee amputation stump may be a useful option and should be considered in clinical situations like this.

Simultaneous superficial venous surgery and on-table subintimal angioplasty in the treatment of venous leg ulcers with arterial compromise.

PURPOSE: To determine the feasibility of synchronous superficial venous surgery and on-table subintimal angioplasty in the treatment of venous ulcers with arterial compromise. METHODS: Between January 1992 and December 2004, 9 patients (8 women; median age 83 years, range 72-92) underwent the synchronous procedure. No patient had deep venous reflux; 4 patients presented with rest pain and 2 were diabetic. Their medical records were retrospectively reviewed to gather data on clinical assessment, ankle-brachial index (ABI), lower limb arterial and venous duplex scans, and treatment variables. RESULTS: Angioplasty was technically successful (median ABI improvement 0.31, range 0.23-0.34) in all procedures, which lasted a median 85 minutes (range 60-160). The procedure was performed under general anesthesia in 7 patients, local in 1, and spinal in 1. Superficial venous surgery was performed first in 8 patients: 6 had great saphenous vein (GSV) ligation without stripping, followed by subintimal angioplasty, and 1 also had small saphenous vein (SSV) ligation. One patient underwent SSV ligation first, followed by angioplasty; another had GSV disconnection and stripping, followed by angioplasty. In 1 patient, angioplasty preceded GSV surgery. One patient required repeat angioplasty 1 week later for re-occlusion. All ulcers healed (median 4 months, range 1-36). Five patients died during a median 32-month follow-up (range 4-82) from unrelated causes; there was 1 ulcer recurrence at 3 years in a patient who declined further investigation and treatment. CONCLUSIONS: Simultaneous superficial venous surgery and on-table subintimal angioplasty is a safe and novel strategy in the management of a select subgroup of patients with venous ulcers and coexistent arterial compromise.

Does carotid endarterectomy lead to a decline in cognitive function or health related quality of life?

Carotid endarterectomy has been shown to reduce the long-term risk of stroke in selected patients. The present study was designed to examine cognitive function and health related quality of life in a series of carotid endarterectomy patients. One hundred and nine patients undergoing carotid endarterectomy were assessed before surgery and at 6 months post op (n = 100) on standard cognitive function tests and quality of life surveys. Microembolisation was detected using transcranial Doppler ultrasonography. Multivariate repeated measures analysis if variance identified evidences of significant impairments on some tests. Further analysis revealed that particulate Microembolisation detected during the procedure was a significant risk factor associated with declining cognitive function. Patients' self-reported health related quality of life had not deteriorated at 6 month following surgery.

Randomized trial of vein versus dacron patching during carotid endarterectomy: long-term results.

BACKGROUND AND PURPOSE: Overviews of randomized patch trials by the Cochrane Collaboration suggest that a policy of routine patching is preferable to routine primary closure. However, there is no systematic evidence that patch type, whether prosthetic or vein, influences outcome after carotid endarterectomy (CEA). METHODS: Two hundred seventy-three patients were randomized to vein or thin-walled Dacron patch (Hemashield Finesse) closure of the arteriotomy after 276 CEA procedures. Patients were reviewed clinically and with duplex ultrasound scanning at 1, 6, 12, 24, and 36 months or until death. No patients were lost to follow-up. Cumulative statistical analyses are presented for the 264 patients (269 CEAs) who actually received a randomized treatment allocation. RESULTS: Cumulative freedom from death or ipsilateral stroke at 3 years (including operative events) was 93.0% in the Dacron patch group and 95.5% in the vein group P =.42). Cumulative freedom from death or any stroke was 91.5% after Dacron patch closure and 93.9% after vein closure (P =.46). Cumulative freedom from recurrent stenosis greater than 70% or occlusion at 3 years was 92.9% for patients randomized to the Dacron patch group and 98.4% for patients randomized to the vein group (P =.03). At 3 years the incidence of stroke in the carotid territory not operated on was 1.0% in 93 patients with no contralateral internal carotid artery disease at randomization, and increased to 1.3% in 78 patients with 1% to 69% stenosis, and 2.0% in 51 patients with contralateral 70% to 99% stenosis. No late strokes occurred distal to 42 occluded contralateral internal carotid arteries. CONCLUSIONS: Patch type has no influence on early operative risk, no association with enhanced patterns of thrombogenicity in the early postoperative period, and no influence on risk for ipsilateral or any stroke at 3 years. Dacron patches were, however, associated with a significantly higher incidence of recurrent stenosis at 3 years, with most occurring within 6 to 12 months of surgery. However, the higher incidence of recurrent stenosis was not associated with a parallel increase in late stroke, and in this study a program of serial ultrasound surveillance could not have prevented one ipsilateral stroke.

Post-traumatic hepatic artery aneurysm--surgical treatment: report of a case.

Hepatic artery aneurysms (HAAs) are uncommon. We present the diagnosis and surgical treatment of a post-traumatic, extrahepatic artery aneurysm.

Simvastatin inhibits human saphenous vein neointima formation via inhibition of smooth muscle cell proliferation and migration.

OBJECTIVE: Migration and proliferation of vascular smooth muscle cells (SMCs) contributes to intimal hyperplasia in saphenous vein (SV) bypass grafts, which leads to patency-threatening stenosis. Evidence for the involvement of basement membrane-degrading matrix metalloproteinases (MMPs) and growth factors in mediating SMC migration and proliferation has been presented in a number of in vitro and in vivo models. 3-Hydroxy-3 methylglutaryl CoA reductase inhibitors (statins) are widely used in patients with atherosclerosis and are claimed to have additional effects beyond cholesterol reduction. We therefore examined the effects of simvastatin, a commonly prescribed statin, on the proliferation and migration of cultured human SV SMC and on neointima formation and MMP activity in human SV organ cultures. To clarify its mode of action, we studied in parallel the effects of a specific MMP inhibitor, marimastat. STUDY DESIGN: Human SV specimens were obtained from patients who underwent coronary artery bypass grafting, and were cultured for 14 days in the presence of three concentrations of simvastatin and subsequently processed for measurement of MMP activity and neointimal thickness measurements. Cultured SV SMCs were used to construct growth curves in the presence of 10% fetal calf serum or 10% fetal calf serum supplemented with simvastatin or marimastat. Migration through a Matrigel basement-membrane matrix (invasion) was quantified with modified Boyden chambers. RESULTS: Simvastatin dose dependently reduced neointima formation (P =.004) in association with reduced MMP-9 activity (P =.03). SMC proliferation and invasion also were inhibited with simvastatin (P <.007 and P <.009, respectively). Marimastat dose dependently inhibited SMC invasion (P <.001) but importantly had no effect on SMC proliferation (P >.36). CONCLUSION: For effective control of neointimal development in vivo, a pharmacologic strategy should inhibit both SMC migration and proliferation. The ancillary properties of 3-Hydroxy-3 methylglutaryl CoA reductase inhibitors typified by simvastatin may be important in this regard.