Stephen A. Badger

A variant in LDLR is associated with abdominal aortic aneurysm

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<1×10−4 were carried through to in silico replication in 1292 AAA cases and 30 503 controls. One single-nucleotide polymorphism associated with P<0.05 after Bonferroni correction in the in silico study underwent further replication (706 AAA cases and 1063 controls from the United Kingdom, 507 AAA cases and 199 controls from Denmark, and 885 AAA cases and 1000 controls from New Zealand). Low-density lipoprotein receptor (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.

The impact of radiation dose exposure during endovascular aneurysm repair on patient safety

OBJECTIVE Endovascular aneurysm repair (EVAR) exposes patients to radiation during the procedure and in subsequent follow-up. The study goal was to calculate the radiation dose in our unit and compare it against other published data and national guidelines. METHODS All EVAR procedures were identified from a prospectively maintained database. Radiation dose, screening time, and volume of intravenous contrast during the procedure were reviewed. Radiation exposure from subsequent computed tomography (CT) imaging was included in the overall exposure. Results are expressed as mean +/- standard deviation. RESULTS From October 1998 to October 2008, 320 elective patients underwent EVAR. Mean screening time was 29.4 +/- 23.3 minutes, and the radiation dose was 11.7 +/- 7.1 mSv. The EVAR was an emergency in 64 patients. The mean screening time was 22.9 +/- 18.2 minutes, and the radiation dose was 13.4 +/- 8.6 mSv. During the first postoperative year, follow-up CT scans exposed the patients to 24.0 mSv, with 8.0 mSv in subsequent years. Abdominal radiographs added an additional 1.8 mSv each year. CONCLUSION EVAR and the follow-up investigations involve substantial amounts of radiation, with well-recognized carcinogenic risks. Because patient safety is paramount, radiation exposure should be minimized. This may be possible by standardizing radiation exposure throughout the United Kingdom by implementing national guidelines and considering other imaging modalities for follow-up.

The effects of abdominal compartment hypertension after open and endovascular repair of a ruptured abdominal aortic aneurysm

OBJECTIVE This study assessed if emergency endovascular repair (eEVR) reduces the increase in intra-abdominal compartment pressure and host inflammatory response in patients with ruptured abdominal aortic aneurysm (AAA). METHODS Thirty patients with ruptured AAA were prospectively recruited. Patients were offered eEVR or emergency conventional open repair (eOR) depending on anatomic suitability. Intra-abdominal pressure was measured postoperatively, at 2 and 6 hours, and then daily for 5 days. Organ dysfunction was assessed preoperatively by calculating the Hardman score. Multiple organ dysfunction syndrome, systemic inflammatory response syndrome, and lung injury scores were calculated regularly postoperatively. Hematologic analyses included serum urea and electrolytes, liver function indices, and C-reactive protein. Urine was analyzed for the albumin-creatinine ratio. RESULTS Fourteen patients (12 men; mean age, 72.2 +/- 6.2 years) underwent eEVR, and 16 (14 men; mean age, 71.4 +/- 7.0 years) had eOR. Intra-abdominal pressure was significantly higher in the eOR cohort compared with the eEVR group. The eEVR patients had significantly less blood loss (P < .001) and transfused (P < .001) and total intraoperative intravenous fluid infusion (P = .001). The eOR group demonstrated a greater risk of organ dysfunction, with a higher systemic inflammatory response syndrome score at day 5 (P = .005) and higher lung injury scores at days 1 and 3 (P = .02 and P = .02) compared with eEVR. A significant correlation was observed between intra-abdominal pressure and the volume of blood lost and transfused, amount of fluid given, systemic inflammatory response syndrome score, multiple organ dysfunction score, lung injury score, and the length of stay in the intensive care unit and hospital. CONCLUSION These results suggest that eEVR of ruptured AAA is less stressful and is associated with less intra-abdominal hypertension and host inflammatory response compared with eOR.

C-reactive protein (CRP) elevation in patients with abdominal aortic aneurysm is independent of the most important CRP genetic polymorphism

OBJECTIVE C-reactive protein (CRP) is a marker of cardiovascular disease. The objective was to determine if abdominal aortic aneurysm (AAA) and CRP serum concentration and its CRP gene are associated. METHODS AND RESULTS AAA patients and AAA negative controls were recruited. CRP concentration was measured and the single nucleotide polymorphism (SNP), rs3091244, assessed. AAA cases were divided into those measuring 30-55 mm and >55 mm in diameter, to assess correlation of CRP with AAA size. A total of 248 (227 male) cases and 400 (388 male) controls were included. CRP concentration was higher in cases (385.0 microl/dL [310.4-442.8] vs 180.3 microl/dL [168.1-196.9]; P < .0001). It was higher in large aneurysms (685.7 microl/dL [511.8-1083.0] vs 291.0 microl/dL [223.6-349.6]; P < .0001), with significant correlation observed to size (r = 0.37, P < .0001). CC was the most common SNP genotype with no difference in distribution (P = .43) between cases and controls. No difference existed in CRP for each genotype in the overall cohort (P = .17), cases (P = .18) and controls (P = .19). CONCLUSION The results demonstrate that CRP production may be related to the presence of AAA, especially in advanced disease. The serum concentration of CRP does not appear to be influenced by the functional SNP of the CRP gene, which also appears to have no association with AAA formation.

Ultrasound is a useful adjunct to mammography in the assessment of breast tumours in all patients

Background:  Ultrasound is the first‐line breast imaging modality in younger patients and an adjunct to mammography in older patients. The objectives of this study were to evaluate the complementary value of ultrasound to mammography in breast cancer and to investigate the use of ultrasound in patients above and below the age of 50 years.

Benefits of a Supervised Exercise Program After Lower Limb Bypass Surgery

This study evaluated the efficacy of an exercise program after arterial bypass surgery. Patients undergoing bypass surgery were randomized to a control group (group I), with standard preoperative and postoperative care, or the intervention group (group II) with a supervised exercise program of twice-weekly treadmill assessments from 4 to 10 weeks postoperatively. Ankle-brachial pressure indices and hemodynamic measurements were recorded before and after exercise. The mean increase of maximum walking distance was 3.8% in group I and 175.4% in group II (P = .001). There was a significant difference between group I and II in the mean ankle-brachial pressure indices increase at the second assessment (0.08 versus 0.23; P = .02). A supervised exercise program leads to better improvement after lower limb bypass surgery for ischemia, but the feasibility of a formal exercise program would be undermined by the reluctance of patients to participate, both in the short-term and long-term.

The Vascular and Biochemical Effects of Cilostazol in Diabetic Patients With Peripheral Arterial Disease

Objectives: Cilostazol improves walking in patients with peripheral arterial disease (PAD). We hypothesized that cilostazol reduces diabetic complications in PAD patients. Methods: Diabetic PAD patients were prospectively recruited to a randomized double-blinded, placebo-controlled trial, using cilostazol 100mg twice a day. Clinical assessment included ankle-brachial index, arterial compliance, peripheral transcutaneous oxygenation, treadmill walking distance and validated quality of life (QoL) questionnaires. Biochemical analyses included glucose and lipid profiles. All tests were at baseline, 6, and 24 weeks. Results: 26 diabetic PAD patients (20 men) were recruited. Cilostazol improved absolute walking distance at 6 and 24 weeks (86.4% vs. 14.1%, P = .049; 143% vs. 23.2%, P = .086). Arterial compliance and lipid profiles improved as did some QoL indices for cilostazol at 6 and 24 weeks. Blood indices were similar at baseline and at follow-up points for both treatment groups. Conclusions: Cilostazol is a well-tolerated and efficacious treatment, which improves claudication distances in diabetic PAD patients with further benefits in arterial compliance, lipid profiles, and QoL.

Risk factors for abdominal aortic aneurysm and the influence of social deprivation.

Introduction: the objective of this abdominal aortic aneurysm (AAA) screening study was to determine attendance and disease prevalence patterns in Northern Ireland and the role of deprivation and other risk factors. Patients and methods: patients from primary care practices from Belfast, Lisburn, and Saintfield were screened. Past medical history and deprivation details were determined. Results: 2264 men from Belfast, 1104 men in Lisburn, and 284 in Saintfield were invited to attend. Overall, 1659 (45.3%) men attended, with 40.6% from Belfast, 55.0% from Lisburn, and 45.8% from Saintfield (P < .0001). Ninety-two (5.5%) new AAAs were diagnosed, with 6.5%, 3.8%, and 6.2% in the 3 areas (P = .055). As deprivation decreased, attendance increased and prevalence decreased. Smoking, peripheral arterial disease, number of medications prescribed, and geographical origin were independent risk factors for AAAs. Conclusion: aneurysm prevalence is influenced by geographical origin and deprivation, which should, therefore, be important factors in health care planning and screening provision.

Surveillance strategies according to the rate of growth of small abdominal aortic aneurysms

The management of small abdominal aortic aneurysms (AAA) is by ultrasound surveillance. The study aimed to calculate their growth rate, identify risk factors and determine appropriate screening intervals. The local screening programme and hospital records were used to identify patients with a small (< 5.5 cm) AAA. The dates and maximum diameter of serial scans of patients with two or more scans were obtained. Patients were subdivided by 0.5 cm increments above 3.0 cm. The rate of growth was calculated by linear regression for each patient using both the absolute measurements and logarithmically (ln) transformed measurements. The 95th centile of growth rate within each subgroup was used to estimate the minimum time to grow to 5.5 cm. A total of 252 were included. The mean (± SD) AAA size on the initial scan was 3.9 (± 0.7) cm. Statin use and initial size were predictive factors for the growth rate. The median rate of growth increased according to size from 0.075 to 0.432 cm/year for AAA < 3.5 cm and > 5.0 cm, respectively. It also steadily increased for ln measurements from 0.022 (or 2.2%/year) to 0.078 or (7.8%/year). The minimum time (months) to reach 5.5 cm was 61, 17, 11 and 5 for AAA < 3.5 cm, 3.5–3.9 cm, 4.0–4.4 cm and 4.5–4.9 cm, respectively. Based on ln measurements, the times were similar at 60, 17, 10 and 4 months. In conclusion, the rate of growth increased steadily with AAA size. An aneurysm < 3.5 cm does not require a repeat scan for 5 years, while those measuring 3.5–3.9 cm and 4.0–4.4 cm require a repeat scan after 17 and 11 months.

Fine needle aspiration at a Regional Head and Neck Clinic: a clinically beneficial and cost-effective service.

Background:  Fine needle aspiration (FNA) is an important adjuvant to the diagnosis of a palpable lesion which often permits the complete assessment of patients. The main objective of this study was to determine the clinical benefit of a dedicated FNA service at a tertiary referral Head and Neck Clinic and to assess if such a service is cost effective.