Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci.

RATIONALE: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. OBJECTIVE: To identify additional AAA risk loci using data from all available genome-wide association studies. METHODS AND RESULTS: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. CONCLUSIONS: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.

A sequence variant associated with sortilin-1 (SORT1) on 1p13.3 is independently associated with abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a common human disease with a high estimated heritability (0.7); however, only a small number of associated genetic loci have been reported to date. In contrast, over 100 loci have now been reproducibly associated with either blood lipid profile and/or coronary artery disease (CAD) (both risk factors for AAA) in large-scale meta-analyses. This study employed a staged design to investigate whether the loci for these two phenotypes are also associated with AAA. Validated CAD and dyslipidaemia loci underwent screening using the Otago AAA genome-wide association data set. Putative associations underwent staged secondary validation in 10 additional cohorts. A novel association between the SORT1 (1p13.3) locus and AAA was identified. The rs599839 G allele, which has been previously associated with both dyslipidaemia and CAD, reached genome-wide significance in 11 combined independent cohorts (meta-analysis with 7048 AAA cases and 75 976 controls: G allele OR 0.81, 95% CI 0.76-0.85, P = 7.2 × 10(-14)). Modelling for confounding interactions of concurrent dyslipidaemia, heart disease and other risk factors suggested that this marker is an independent predictor of AAA susceptibility. In conclusion, a genetic marker associated with cardiovascular risk factors, and in particular concurrent vascular disease, appeared to independently contribute to susceptibility for AAA. Given the potential genetic overlap between risk factor and disease phenotypes, the use of well-characterized case-control cohorts allowing for modelling of cardiovascular disease risk confounders will be an important component in the future discovery of genetic markers for conditions such as AAA.

Correlation of ABCD2 score with degree of internal carotid artery stenosis: an observational pilot study.

BACKGROUND: ABCD(2) is a validated scoring system that predicts the risk of stroke after a transient ischemic attack (TIA). International guidelines suggest that patients with a low score can be investigated on an outpatient basis. The ABCD2 score, however, cannot identify which patients have significant internal carotid artery (ICA) disease, and this group of patients could benefit from rapid access carotid endarterectomy (RACE). Studies have shown that patients with significant carotid artery disease have a higher risk of neurologic events or recurrent stroke. The aim of this study was to document the range of ABCD2 scores in patients with carotid artery-related TIA, and investigate any correlation between the ABCD2 scores and ICA stenosis. METHODS: Patients undergoing carotid duplex ultrasound scan for TIA from January 2009 to May 2010 from two vascular units were identified from the vascular database retrospectively. Clinical notes were reviewed and outcomes measures were recorded: ABCD2 scores (age, blood pressure, clinical features, diabetes, and duration) and carotid plaque morphology. RESULTS: Ninety-seven patients with a mean age of 74 (range 56-90) years had ICA stenoses of ≥50% up to 100%. Fifty-seven patients had an ABCD2 score of ≤4. There was no significant correlation between ABCD2 scores and degree of ICA stenosis nor carotid plaque morphology (P=0.2, r=1.0, and P=1.0, r=0.0007, respectively). CONCLUSIONS: Because no correlation between ABCD2 scores and the degree of ICA stenosis was found, all patients with carotid territory TIA should undergo urgent imaging of the carotid arteries because a high proportion of these patients may benefit from RACE.

The Effect of Vacuum-assisted Closure on the Tissue Oxygenation of Venous Ulcers: A Pilot Study .

UNLABELLED: Background. Vacuum-assisted closure (V.A.C.® Therapy, KCI, San Antonio, TX) has been widely used to increase the healing rate of a variety of wounds. It has been hypothesized that one of the actions of VAC is to increase perfusion and subsequent oxygenation of tissue. The aim of the present study was to investigate the effect of VAC therapy on transcutaneous oximetry measurements (TCOM) of skin surrounding chronic venous ulcers. METHODS: This was a prospective, experimental pilot study. Patients undergoing compression therapy were recruited from a community wound clinic. All patients had ankle-brachial pressure indices (ABPI) > 0.8. Three TCOM values were taken from around the ulcer and a reference TCOM was taken from the chest. Negative pressure was applied on the ulcer at 125-mmHg continuous subatmospheric pressure and four-layer compression bandaging over the VAC drapes. The duration of the study was 6 days. On day 6, dressings were removed and TCOM was repeated at the same skin sites. RESULTS: Fourteen of the 17 patients completed the trial. The median age was 73 years (range 49-85). No significant difference was found in oxygen partial pressure pre-and post-VAC therapy around the ulcer site (mean 41.5 mmHg versus 40 mmHg [P = 0.67]). There was a significant difference in TCOM between the reference point and the periwound area (mean 60.5 versus 40 [P < 0.0005]). CONCLUSION: This pilot study suggests that VAC therapy does not change oxygen partial pressure around venous ulcers. TCOM of the skin around ulcers were low despite normal ABPIs.

Use of autopsy in general surgery: a comparison of practice and opinion.

OBJECTIVE: To examine current practice regarding autopsy requests and assess consultant opinion regarding the role of autopsy in a general surgical department. METHODS: One hundred deaths that occurred in a teaching hospital general surgical department, over a 2-year period, were randomly selected. After review of the hospital notes, a brief summary of each admission was distributed to all 13 consultant general surgeons in the department. Surgeons were asked to comment whether each case should have been discussed with the coroner, whether a coroner's autopsy should have been carried out, whether a hospital post-mortem examination should have been carried out and whether it would be appropriate to complete a death certificate without a post-mortem examination. Surgeon responses were compared with actual outcomes, and both were analysed for predictors of variation in practice. RESULTS: The majority of patients were elderly (median age 79 years, 49% >80 years), were admitted acutely (92%) and did not undergo an operation (73%). Thirty-three patients died of cardiac or respiratory causes. Patients who had undergone a recent operation were more likely to be referred to the coroner (P < 0.001) and more likely to undergo coroner's autopsy (P = 0.011). Older patients and those admitted from a rest home were less likely to be referred to the coroner (P < 0.001 and 0.02, respectively) or undergo coroner's autopsy (P = 0.002 and 0.011, respectively). The survey predicted more referrals to the coroner (44 vs 30, P = 0.001) and more hospital autopsies (21 vs 2, P < 0.001) and that the treating doctor would complete the certificate of death less often than actually happened (79 vs 91, P = 0.004). The survey suggested that surgeons were more likely to complete the certificate of death in patients with active malignancy (P = 0.01), but this was not observed in practice. CONCLUSIONS: General surgeons consider autopsy to be necessary more often than that is taking place in practice in our institution. The continued decline in autopsy rates may compromise the safety and quality of the service provided by general surgeons and result in a gap in the education of surgeons and trainees.

Composition of volatile organic compounds in diathermy plume as detected by selected ion flow tube mass spectrometry.

BACKGROUND: There is some evidence that surgical plume may pose a risk to health professionals, but the risks posed by volatile organic compounds have not been thoroughly investigated. METHODS: The composition of volatile organic compounds in diathermy plume produced during surgery was analysed by selected ion flow tube mass spectrometry. RESULTS: Hydrogen cyanide (3-51 parts per million), acetylene (2-8 parts per million), and 1,3-butadiene (0.15-0.69 parts per million) were identified in the plume. CONCLUSION: Although there is no evidence of adverse health effects from the volatile organic compound in diathermy plume, the evidence that it is safe to breathe this plume is lacking. Therefore, we would recommend the use of smoke evacuators where practical.

Antiplatelet therapy in peripheral occlusive arterial disease.

BACKGROUND: Antiplatelet therapy (APT) in patients with peripheral occlusive arterial disease (POAD) may reduce cardiovascular (CV) morbidity and mortality by inhibiting atherothrombosis. This article reviews the current evidence for APT in patients with stable POAD and in patients undergoing revascularization procedures for POAD. METHODS: A Medline and Pubmed literature search (January 1966 to February 2003) was conducted to identify articles relating APT and POAD. Manual cross referencing was also used. RESULTS AND CONCLUSIONS: Meta-analyses suggest that APT (most commonly aspirin) in patients with stable POAD significantly reduces the incidence of nonfatal stroke, myocardial infarction and CV death. However, this conclusion is based on subset analysis of data predominantly involving patients with coronary and cerebrovascular atherosclerosis. There is a little direct evidence for the use of aspirin in patients with isolated POAD, but in practice, aspirin remains the most commonly used antiplatelet agent as high rates of coronary and cerebrovascular diseases are observed in this patient population. For patients with POAD without additional indicators of vascular risk, the protective effect of aspirin is unclear and dependent on the balance of risks and benefits in the individual patient. For patients undergoing peripheral revascularization, ticlopidine and aspirin in combination with dipyridamole are effective in maintaining patency after bypass procedures and following angioplasty/femoral endarterectomy. The efficacy of thienopyridines in peripheral angioplasty is uncertain, and the optimum timing and duration of APT relative to intervention are not known.

Point of care testing of aspirin resistance in patients with vascular disease.

INTRODUCTION: The reported range in rates of aspirin resistance (5.5-60%) may reflect difficulties in studying platelet function and the variety of tests used. This study used a platelet function analyzer (PFA-100) to prospectively document aspirin resistance in a cohort of patients with arterial disease. METHODS: Patients with internal carotid artery (ICA) stenosis or intermittent claudication (IC) were recruited. Exclusion criteria were contraindications to aspirin, prescription of other medication with known antiplatelet effects or known platelet abnormalities. After prescription of 100 mg aspirin/day for 2 weeks an uncuffed venous blood sample was taken and analysed with the PFA-100. Aspirin resistance was defined as closure time (CT) less than the upper limit of normal (158 s collagen/epinephrine agonist; 118 s collagen/adenosine diphosphate (ADP) agonist). RESULTS: Thirty-three patients with IC and 12 patients with ICA stenosis were recruited (n = 45). Median (range) age was 74 years (49-85) and the male to female ratio was 1.5:1. The median (range) CT was >300 (85 to >300) s with collagen/epinephrine and 100 (52 to >300) s with collagen/ADP agonist. Twelve patients (27%) in the collagen/epinephrine group had normal CT despite treatment with 100 mg aspirin, indicating resistance. Of the 33 patients with collagen/epinephrine CT prolonged by aspirin, 10 patients also had prolonged collagen/ADP CT, suggesting excessive platelet inhibition. CONCLUSION: A significant proportion of patients taking aspirin do not show laboratory evidence of platelet inhibition and may not be protected from atherothrombotic events. The PFA-100 appears to be a useful tool to screen for both aspirin resistance and excessive aspirin mediated platelet inhibition.

Preoperative cardiac assessment for patients with infrarenal abdominal aortic aneurysms: a survey of current practice by vascular surgeons in New South Wales and Australian Capital Territory.

BACKGROUND: The reported mortality rate following open elective repair of abdominal aortic aneurysm (AAA) varies between 0 and 12%. Much of the mortality and major morbidity is caused by cardiac events. The evidence regarding best practice for cardiac assessment and optimization of this patient group is unclear. The aim of the present study was to evaluate current practice of cardiac risk factor assessment by vascular surgeons in New South Wales (NSW) and Australian Capital Territory (ACT) for patients undergoing open elective repair of infrarenal AAA. METHODS: A postal questionnaire was sent to 46 surgeons in NSW and ACT identified as expressing a principal or major interest in vascular surgery. If no response was received within 3 weeks, a second questionnaire was sent and if no response was received after the second mailing, a telephone survey of non-responders was conducted. Data were collated regarding the importance of risk factors elicited by clinical history, preoperative investigation, referral for cardiological opinion, use of perioperative beta-blockade and the timing of aortic surgery in relation to coronary artery revascularization and acute myocardial infarction. RESULTS: The overall response rate was 87% (40/46) and the median (range) response time was 14 (4-109) days. Only 22 of 40 and 23 of 40 surgeons consider diabetes mellitus or renal impairment, respectively, to be important when assessing cardiac risk and 34 of 40 surgeons do not employ a validated risk index in preoperative assessment. Sixteen of 40 surgeons refer all patients needing AAA repair to a cardiologist, while 24 of 40 would initiate cardiac investigations themselves (either stress electrocardiography, scintigraphy or echocardiography). Seventeen surgeons always or usually commenced perioperative beta-blockade with wide variations in the commencement (1 to > 28 days preoperatively) and duration (< 1 week to > 28 days postoperatively) of treatment. The timing of AAA repair following coronary revascularization ranged from < 1 week to 6 months and delay in surgical repair of AAA following myocardial infarction ranged from < 1 week to > 6 months. CONCLUSION: Preoperative assessment of cardiac risk in patients for repair of AAA lacks consensus among vascular surgeons in NSW and ACT. The diversity of clinical practice may rest with the paucity of prospective trials published in the medical literature or the influence of local institutional facilities.

Patient flow to carotid endarterectomy: hastening the patient journey.

BACKGROUND: Early carotid endarterectomy (CEA) after stroke or transient ischaemic attack is the proposed standard of care to prevent recurrent ischaemic events in selected patients. The aim of this study was to investigate if this standard is achieved in a tertiary vascular unit. METHODS: This was a clinical audit. CEAs performed from 1 January 2006 to 31 December 2008 at Christchurch hospital were identified. The value stream from initial presentation to surgery was mapped in two phases (phase 1; 2006-2007 and phase 2; 2008). Patients who had carotid intervention for asymptomatic carotid lesions were excluded. RESULTS: The relevant patient journey was documented in 81 patients (55 phase 1; 26 phase 2). Median time from initial presentation to carotid ultrasound was 5 days in phase 1 and 6 days in phase 2. Time from presentation to vascular surgery review was 22 days in phase 1 and 13 days in phase 2. Time from presentation to CEA significantly reduced from 83 to 32 days between phases (P < 0.005). CONCLUSIONS: There has been a significant decrease in time from presentation to operation between phase 1 and 2. The most significant change is reduced delay between vascular surgery review and CEA. There has been no improvement in urgency of referral for imaging or surgical review. This part of the patient journey is a target for improvement.

Delays in discharge of vascular surgical patients: a prospective audit.

AIM: To quantify delays in discharge for vascular surgical patients and identify causes of such delays. METHODS: A prospective audit of delays in discharge of vascular surgical admissions over a 6-month period was performed. Expected date and time of discharge was compared with actual date and time of discharge. Day-case patients, patients who died during admission and patients not under the direct care of the vascular team were excluded. RESULTS: There were 99 elective and 51 acute admissions accounting for 729 hospital bed days. The median (range) age was 72 years (21-92) and 94% of patients were living independently in the community. Forty-seven percent of patients were discharged on the planned day and time, 21% on the planned day but at a later-than-predicted time and 32% were delayed by more than 1 day. Delays identified in this audit accounted for 135 bed days. Fifteen percent of delays were due to causes that can be improved by internal organization (e.g. delayed paperwork). The majority of the delays (85%) were due to external factors such as lack of rehabilitation beds or lack of placement facilities in nursing homes. Elderly patients and acute admissions were more likely to have long delays in discharge. CONCLUSION: Delays in discharge of vascular surgical patients use a lot of acute surgical bed days. Strategies to prevent delays in discharge should include not only improving internal organization and early identification and referral of patients who require rehabilitation/placement but also increased funding for such essential non-acute services.

Net-based information on varicose vein treatments: a tangled web.

AIMS: 30-40% of individuals will be affected by varicose veins during their lifetime. Many will contemplate treatment and will access the (Inter)net for information. The aim of this study is to determine whether New Zealand-based websites are an accurate source of information for the public. METHODS: Inclusion criteria were New Zealand based websites that contained information on varicose vein treatments. These websites were identified using the search-engines Google and Yahoo. The first 60 websites from each were evaluated and subdivided into 4 groups based on web-site ownership: (1) Vein clinic/hospital; (2) Appearance medicine; (3) Online stores; (4) Health editorials; and (5) Medical resources. RESULTS: 46 of the 120 websites satisfied the inclusion criteria. 18 websites (39%) explained what varicose veins were. Information about treatment options was most comprehensive in the "Vein clinic/hospital" group. The "Appearance medicine" group mostly contained information on outpatient interventional therapies. "Health editorial" sites had lifestyle modification options. All the online herbal/health stores mentioned herbal treatment options. CONCLUSION: Few websites fully informed patients about treatment options while some simply advertised non-evidence based treatments. This study suggests that the Internet is not a reliable source of information and does not accurately inform patients about varicose veins and the treatment options.

Who do you want to treat your varicose veins?

The management of varicose veins is evolving at pace but the speed of change often outstrips the evidence. Patients should expect to be offered the whole range of treatment options that are suitable for their particular circumstances. This range should include conservative management, surgery, endovenous ablation techniques, and ultrasound guided sclerotherapy. If all the options are not discussed, patients should ask why.

Quality of clinical notes for vascular surgery admissions: a CRABEL score review.

AIM: To compare the quality of patient notes between acute and elective admissions in vascular surgery. METHOD: Patient notes from the 50 most recent acute and elective admissions on a vascular surgical unit were reviewed using the CRABEL score. Points for quality of record keeping were awarded in four categories: Initial Clerking, Subsequent Entries, Consent and Discharge Summary. Total scores were calculated as a percentage. One hundred per cent represents the minimum quality standard expected. Overall CRABEL scores were compared for differences in the quality of note keeping between acute and elective admissions. Further analysis identified areas that need improvement. RESULTS: The mean CRABEL score for acute admissions was 79.2% (77.0-81.3, 95% C.I.) compared to 81.3% (78.8-83.8, 95% C.I.) for elective admissions (t-test P= n.s.). When the individual categories were analysed no statistically significant difference was observed between the two groups for 'Subsequent Entries' and 'Consent' sections (t-test p= n.s.). 'Initial Clerking' category scored significantly better for elective 16.3 out of 20 (15.7-16.9, 95% C.I.) admissions compared to acute admissions 14.6 out of 20 (13.9-15.3, 95% C.I.), (t-test P= 0.00063). 'Discharge Summary' section also scored significantly better for elective admissions 9.9 out of 10 (9.9-10.0, 95% C.I.) compared to acute admissions 9.6 out of 10 (9.3-9.9, 95% C.I.), (t-test P= 0.040). CONCLUSION: There was no statistically significant difference in the overall quality of written patient notes between acute and elective admissions, however 'Initial Clerking' and 'Discharge Summary' were better documented for elective admissions. Both acute and elective admissions were observed to have substandard quality of record keeping.

Topical negative pressure wound therapy (TNPWT): current practice in New Zealand.

AIM: To survey current opinion, regarding TNPWT, from New Zealand vascular surgeons. METHOD: Registered vascular surgeons currently practicing in New Zealand were identified from the Vascular Society of New Zealand (VSNZ) database. A questionnaire was emailed asking if they used TNP in their vascular surgical practice and whether or not they considered themselves 'up to date' regarding published evidence for TNP. Surgeons were also asked how often and how successful they felt that TNP was in different clinical situations (arterial ulcers [after revascularisation]; venous ulcers; mixed arterial/venous ulcers; following debridement of the 'diabetic (Db) foot'; lower limb (LL) surgical wound infections/dehiscences; and lymphocoeles/seromas/lymph fistulas not treated successfully with conservative management). One email reminder, followed by a hard copy reminder was sent to those who failed to respond to the first email. RESULTS: Of 38 vascular surgeons 34 responded (89.5%). Median response time was 3.38 days (range 12 min-11.8 days). 28 (82%) vascular surgeons used TNP in their NZ clinical practice. 17 (50%) considered themselves up to date regarding published evidence, 8 (23.5%) admitted to not being up to date with the evidence and 9 (26%) did not know. TNP appears to be used most frequently and with most success following debridement of diabetic foot wounds and in the management of infected/dehisced surgical wounds. CONCLUSION: TNPWT is widely used by NZ vascular surgeons, despite many not considering themselves up to date regarding published evidence. It is most favoured for treating diabetic feet post debridement and for lower limb surgical wounds.

Diastasis recti and abdominal aortic aneurysm.

An association between abdominal aortic aneurysm (AAA) and abdominal wall hernia has been suggested, possibly reflecting a common collagen disorder. The same mechanism may also cause a greater frequency of diastasis recti among patients at risk of developing AAA. Diastasis recti could be used to identify patients at risk of AAA, with implications for AAA screening. The aim of this study was to determine whether an association between diastasis recti and AAA could be demonstrated.The preoperative computed tomographic (CT) scans of 75 male patients undergoing elective AAA repair were retrospectively examined and linea alba width recorded at supraumbilical and subumbilical levels. Measurements were compared with controls frequency matched for age.Fifty patients with AAA were observed to have supraumbilical diastasis recti on preoperative CT compared with 47 controls. Mean linea alba width was not significantly different between the two groups at either the supraumbilical (19.3 mm vs 20.7 mm, p = .45) or subumbilical (3.6 mm vs 4.3 mm, p = .43) level.The findings do not support the hypothesis that the presence of diastasis recti can serve as an indication to select male patients for screening for AAA.