Hany Hafez

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.

Background: Intracranial aneurysms ( IAs ), abdominal aortic aneurysms ( AAAs ), and thoracic aortic aneurysms ( TAAs ) all have a familial predisposition. Given that aneurysm types are known to co‐occur, we hypothesized that there may be shared genetic risk factors for IAs , AAAs, and TAAs . Methods and Results: We performed a mega‐analysis of 1000 Genomes Project‐imputed genome‐wide association study ( GWAS ) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA , AAA , and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA ‐, AAA ‐, and TAA ‐associated SNP s and tested these scores for association to case‐control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium–score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single‐nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls ( IA ) and 4391 cases and 37 904 controls ( AAA ), and found nominally significant associations for IA risk locus 18q11 near RBBP 8 to AAA (odds ratio [ OR ]=1.11; P =4.1×10 ⁻⁵ ) and for TAA risk locus 15q21 near FBN 1 to AAA ( OR =1.07; P =1.1×10 ⁻³ ). Conclusions: Although there was no evidence for polygenic overlap between IAs , AAAs , and TAAs , we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs . These two loci will require further replication.

Background—: Abdominal aortic aneurysm (AAA) is a common cardiovascular disease among older people and demonstrates significant heritability. In contrast to similar complex diseases, relatively few genetic associations with AAA have been confirmed. We reanalyzed our genome-wide study and carried through to replication suggestive discovery associations at a lower level of significance. Methods and Results—: A genome-wide association study was conducted using 1830 cases from the United Kingdom, New Zealand, and Australia with infrarenal aorta diameter ≥30 mm or ruptured AAA and 5435 unscreened controls from the 1958 Birth Cohort and National Blood Service cohort from the Wellcome Trust Case Control Consortium. Eight suggestive associations with P −4 were carried through to in silico replication in 1292 AAA cases and 30 503 controls. One single-nucleotide polymorphism associated with P LDLR ) rs6511720 A was significantly associated overall and in 3 of 5 individual replication studies. The full study showed an association that reached genome-wide significance (odds ratio, 0.76; 95% confidence interval, 0.70–0.83; P =2.08×10 ⁻¹⁰ ). Conclusions—: LDLR rs6511720 is associated with AAA. This finding is consistent with established effects of this variant on coronary artery disease. Shared causal pathways with other cardiovascular diseases may present novel opportunities for preventative and therapeutic strategies for AAA.

Aims: To review the results and cost of a rolling ultrasound-guided foam sclerotherapy (UGFS) treatment programme for patients with chronic superficial venous insufficiency. Method: A prospective study of a rolling treatment programme where patients were offered unlimited follow-up at intervals of 6–8 weeks and further (top up) UGFS when necessary, until occlusion criteria were met. Results: A total of 213 lower limbs with complete follow-up were included in the study. Median (range) age was 57 (16–94) years, maximum diameter of varicose vein was 10 (3–18) mm, C of CEAP (clinical, aetiological, anatomical and pathological elements) was 4 (2–6), number of treatment sessions was one (1–4) and follow-up was three (1.5–33) months. Satisfactory occlusion could not be achieved in nine (4%) limbs. The ratio of odds (95% CI) for requiring more than one treatment session was 3.58 (1.46–8.77), P = 0.002 for great saphenous varicosity and 2.11 (1.13–3.94), P = 0.015 for age 50 or more. There were 20 (9.3%) immediate and 63 (29.5%) delayed adverse effects. All were minor except for one cutaneous nerve injury, one pulmonary embolism and one infected haematoma. The ratio for odds (95% CI) for post-treatment skin discolouration was 2.59 (1.14–5.87), P = 0.017 for women and 1.32 (1.02–1.71), P = 0.032 for increasing sclerosant volume used. Service line costing per completed treatment episode was £115.22 (€130.07, $188.60). Conclusion: UGFS in a rolling treatment programme is safe and can achieve high occlusion rates at a low cost. Patients above the age of 50 with great saphenous varicosity are likely to require more than one treatment session.