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.

Prospective study of natural history of deep vein thrombosis: early predictors of poor late outcomes.

BACKGROUND: A proportion of patients with deep vein thrombosis (DVT) will develop postthrombotic syndrome (PTS). Currently, the only clearly identified risk factors for developing PTS are recurrent ipsilateral DVT and extensive proximal disease. The aim of the study was to assess the natural history of DVT and identify early predictors of poor clinical outcome at 5 years. METHODS: Patients with suspected acute DVT in the lower limb were assessed prospectively. All patients with a confirmed DVT were asked to participate in this study. Within 7-10 days after diagnosis of DVT, patients underwent a further review, involving clinical, ultrasound, and air plethysmography assessment of both lower limbs. Patients were reassessed at regular intervals for 5 years. RESULTS: One hundred twenty-two limbs in 114 patients were included in this study. Thrombus regression occurred in two phases, with a rapid regression between 10 days and 3 months, and a more gradual regression thereafter. Reflux developed as thrombus regression occurred. Segmental reflux progressed to axial deep reflux and continued to deteriorate in a significant proportion of patients with iliofemoral-popliteal-calf DVT throughout the 5-year study period. Similarly, venous filling index became progressively more abnormal, in this group, over the course of the study. Four risk factors for PTS were identified as best predictors: extensive clot load on presentation; <50% clot regression at 6 months; venous filling index >2.5 mL/sec; and abnormal outflow rate (<0.6). Patients with three or more of these risk factors had a significant risk of developing PTS with sensitivity 100%, specificity 83%, and positive predictive value 67%. Patients scoring 2 or less did not have PTS at 5 years with a negative predictive value of 100%. CONCLUSIONS: This is the first study to show that venous assessment at 6 months post-DVT can predict PTS at 5 years. Those who will not develop PTS can be reassured of this at 6 months.

A simple quality of life questionnaire for patients with faecal incontinence.

INTRODUCTION: A simple quality of life questionnaire was designed to triage patients with faecal incontinence to the most appropriate level of support, investigation and treatment. METHOD: A questionnaire was developed to include a 'symptom' score, similar in content to St Mark's questionnaire and a 'bothersome' score. A pilot study (34 patients) assessed the clarity of questions. Once content validity was established, it was sent to 360 patients who attended a pelvic floor clinic. Its external validity was assessed against the established standards of the short form 36 (SF-36) and the Manchester Health Questionnaires. Ease of use for these was assessed using a separate form. RESULTS: Of the 360 patients, 86 replied. The questionnaire was shown to be reliable both by measurement of its internal consistency and by test-retest analysis. There was a significant correlation between the scores of the new questionnaire and the Manchester Health Questionnaire as well as the SF-36. Divergence validity, assessed by correlating the number of pads used and the overall symptom score, was established. The new questionnaire was easiest to complete, taking on average 4 min. CONCLUSION: We have demonstrated that the new questionnaire is reliable and valid. It is easy and quick to complete and assesses both severity and impact of symptoms.

Spontaneous intracerebral haemorrhage: a rare complication of aortic aneurysm endoleak.

We present a rare case of intracerebral haemorrhage secondary to consumptive coagulopathy in relation to ongoing endoleak after thoracic endovascular aneurysm repair (TEVAR). A 68-year-old man underwent elective TEVAR for an 18 cm diameter Crawford type II thoracoabdominal aneurysm. He was subsequently shown to have a type 1b endoleak and a short episode of disseminated intravascularcoagulation (DIC) perioperatively. Two months after the procedure, he experienced a consumptive coagulopathy leading to intracerebral haemorrhage and ultimately his death. Endoleak-related DIC is an underappreciated phenomenon within the medical literature. Currently, management is reliant on general DIC principles and anecdotal experiences of others within the case report literature.

Accuracy and repeatability of the Dopplex Ability.

BACKGROUND: Ankle-brachial index (ABI) and pulse volume recordings (PVR) are non-invasive tests used in diagnosis of peripheral arterial disease (PAD). The Dopplex Ability is an automated ABI/PVR device utilising air plethysmography, offering easy and rapid PAD diagnosis. The accuracy and repeatability of the Dopplex were assessed in comparison to the Doppler/air plethysmography-based Parks Flo-Lab system. METHODS: Sixty-six patients (n = 129 lower limbs) were assessed with both Dopplex and Parks systems. For Dopplex ABI and PVR to be deemed accurate, it had to be within ±10% of the Parks ABI, and the PVR grade (1-4) had to be equal. The coefficient of variation (CV) was calculated from three repeat ABI/PVR readings to assess repeatability. RESULTS: The Dopplex and Parks devices correlated poorly for ABI (R2 = 0.17) with only 43% of ABIs and 69% of PVRs meeting the accuracy criteria compared to the Parks values. The specificity and sensitivity were 56% and 82%, respectively for ABI, and 91% and 89%, respectively for PVRs. The Dopplex showed a significantly higher CV for both ABIs and PVRs compared to the Parks. CONCLUSION: We found the Dopplex device to demonstrate suboptimal accuracy and repeatability in assessing ABI/PVR, and it was deemed unsuitable for use in our community.

Emergency EVAR for ruptured abdominal aortic aneurysms: New Zealand experience.

AIM: A ruptured abdominal aortic aneurysm (rAAA) remains a significant threat to life, with a 30-50% in-hospital mortality rate. The recent introduction of emergency endovascular aneurysm repair (rEVAR) in New Zealand presents an alternative to open repair for rAAAs. The aim of this paper is to review the current experience in New Zealand in the repair of rAAAs. METHODS: Data from the Australasian Vascular Audit (AVA) was reviewed, with data pertaining to rAAAs collected for the five-year period from January 2010 to December 2014. RESULTS: Two hundred and eighty-five rAAAs were reported over the five-year period, with an overall mortality rate of 34.0%. There was no significant difference in in-hospital mortality rates alone after rEVAR vs open repair (rOR) (OR 0.39, 95% CI 0.14-1.06, P=0.065). Significant reductions in length of hospital stay (9.710.2 days vs 16.812.9 days, P=0.0125) and the combined in-hospital mortality/post-operative complication rate (35.7% vs 63.6%, OR 0.3, 95% CI 0.1-0.7, P=0.005) were observed after rEVAR vs rOR. CONCLUSION: A primary rEVAR approach is appropriate in selected patients and may represent a paradigm shift in the management of ruptured AAAs in New Zealand.