Insulin-like growth factor I - a novel biomarker of abdominal aortic aneurysms.

OBJECTIVE: The study aimed to test the potential role of insulin-like growth factor I (IGF-I) and IGF-II as biomarkers for abdominal aortic aneurysm (AAA). METHODS AND RESULTS: IGF-I and II levels were analysed in 115 patients with screening diagnosed AAA kept under annual surveillance for 10 years. Serum IGF-I correlated positively with AAA size and growth rate (r = 0.23, P = 0.016 and r = 0.27, P = 0.004), persisting after adjustment for potential confounders. Serum IGF-I level predicted cases needing later surgery (AOC: 0.63; 95% confidence interval: 0.52-0.73). CONCLUSIONS: In this prospective, long-term study, baseline serum IGF-I correlated positively with AAA size and growth rate and predicted future need for preventive surgery.

Atrial fibrillation and upper limb thromboembolectomy: a national cohort study.

BACKGROUND: The risk factors associated with, and the incidence of systemic embolism in patients with atrial fibrillation (AF) are poorly understood. OBJECTIVES: We studied the association between AF and upper limb thromboembolectomy involving brachial, ulnar or radial artery in a national cohort study that included all individuals aged 40-99 years with incident AF. METHODS: Data were retrieved from the Danish National Vascular Registry, the National Registry of Patients, the Danish Civil Registration System and Statistics Denmark. RESULTS: In total, 131,476 patients (68,042 men and 63,434 women) with AF without previous thromboembolectomy in the upper limb were registered. In the study cohort, 130 men underwent upper limb thromboembolectomy over 220,890 person-years of observation, whilst 275 women underwent thromboembolectomy over 197,777 patient-years. The incidence per 100,000 person-years was 58.9 (95% CI, 49.2-69.8) for men and 139.1 (95% CI, 123.1-156.5) for women. The relative risk of thromboembolectomy among patients with AF compared to the background population was 7.5 (95% CI, 6.3-8.9) for men, and 9.3 (95% CI, 8.3-10.5) for women. Women with AF had a relative thromboembolectomy risk of 1.8 (95% CI, 1.5-2.3) compared to men with AF. Among patients with AF, history of hypertension (HR 2.2-2.9), myocardial infarction (HR 2.9-3.9), heart failure (HR 1.6-1.9) and stroke (HR 2.2-3.8) were significantly associated with increased risk of thromboembolectomy in both men and women. CONCLUSIONS: AF substantially increases the risk of upper limb thromboembolectomy. This risk is higher with increasing age, female gender, and associated with hypertension, myocardial infarction, heart failure and stroke.

Upper-limb thrombo-embolectomy: national cohort study in Denmark.

OBJECTIVES: We investigated the incidence of thrombo-embolectomy in upper-limb and prognosis with respect to arm amputation, stroke and death. METHODS: We performed a national cohort study of individuals, aged 40-99 years, and undergoing first-time thrombo-embolectomy in the brachial, ulnar or radial artery in Denmark from 1990 to 2002. The data were retrieved from the National Vascular Registry and from the National Registry of Patients and the Civil Registration System. Patients were followed until 2006 to ascertain the occurrence of amputation and stroke and until 2007 with respect to death. RESULTS: In total, 1377 incident cases of thrombo-embolectomy were registered, comprising 504 (36.6%) males with a mean age of 72.0 (standard deviation (SD) 12.4) years and 873 (63.4%) females with a mean age of 77.2 (SD 11.7) years. Incidence was 3.3 (95% confidence interval (CI): 3.1-3.7) for males and 5.2 (95% CI: 4.9-5.6) for females per 100000 person-years. After thrombo-embolectomy, upper-limb amputation was performed in 11 (incidence 2.2%; 95% CI: 1.2-3.4) males and 31 (3.6%; 95% CI: 2.5-4.9) females. Age- and sex-specific risk of stroke was 2-16 times higher, and risk of death 3-11 times higher, than in the general population. CONCLUSIONS: Upper-limb thrombo-embolectomy is associated with an increased risk of limb amputation, stroke and death.

Long-term benefit and cost-effectiveness analysis of screening for abdominal aortic aneurysms from a randomized controlled trial.

BACKGROUND: The aim was to estimate long-term mortality benefits and cost-effectiveness of screening for abdominal aortic aneurysm (AAA) in men aged 64-73 years. METHODS: All men aged 64-73 years living in Viborg County were randomized to be controls (n = 6306) or invited for abdominal ultrasonography at a regional hospital (n = 6333). Mortality and AAA-related interventions were recorded in national databases. The cost of initial screening was based on actual costs of the programme. Incremental cost-effectiveness ratios (ICERs) were calculated on gains in life years and Quality Adjusted Life Years (QALY). Discounting (3 per cent) was applied to both costs and effects, and all costs were adjusted to euros at 2007 prices. RESULTS: The relative risk reduction of the screening programme in AAA-related mortality was 66 per cent (hazard ratio 0.34, 95 per cent confidence interval (c.i.) 0.20 to 0.57). The corresponding risk reduction in all-cause mortality was 2 per cent (hazard ratio 0.98, 95 per cent c.i. 0.93 to 1.03). The ICER was estimated at euro157 (-3292 to 4401) per life year gained and euro179 (-4083 to 4682) per QALY gained. Screening was found to be cost effective at a probability above 0.97 for a willingness-to-pay threshold of only euro5000. One-way sensitivity analysis demonstrated that this result was robust to various alternative assumptions, as the probability did not drop below 0.90 for any scenario. CONCLUSION: The mortality benefit of screening for AAA in men aged 64-73 years was maintained in the longer term and screening was cost effective.

Potential circulating biomarkers for abdominal aortic aneurysm expansion and rupture--a systematic review.

BACKGROUND: The maximal diameter of abdominal aortic aneurysms (AAAs) is the dominating indication for repair. However half of the AAAs repaired would never have ruptured if left unrepaired, although small AAAs occasionally rupture. Earlier surgery may be associated with a lower mortality. More precise indicators for surgery are warranted. This systematic review identifies potential systemic biomarkers for AAA rupture or expansion. METHODS: MEDLINE/PubMed and EMBASE (from 1985 trough May 2007) were searched with the medical subject heading abdominal aortic aneurysm and keywords "size", "progression" or "growth" or "expansion rate" or "rupture" on the basis of MESH tree and as a text search restricted to English, German, French and Italian. In addition, reference lists were studied and manual searches performed. Observational studies investigating the association of circulating biomarkers with AAA rupture, expansion or size were selected. DATA EXTRACTION: Two reviewers (SU and GU) independently extracted the following data: year of publication, study characteristics, duration of follow-up, circulating biomarker, AAA expansion rate or size or rupture. RESULTS: 699 papers were identified. After exclusion of thoracic aneurysms and cardiac studies (n=118), surgical or medical treatment studies (n=179), case reports and animal studies (n=87), as well as reviews or letters (n=66), 249 articles were selected. Also excluded were 230 papers that did not report AAA size, expansion rate or rupture. 39 papers were included. Several potential biomarkers were identified. The strongest association with AAA was obtained with serum elastin peptides (SEP) and plasmin-antiplasmin (PAP) complexes. Matrix-degrading metalloproteinase 9 (MMP9) and interferon-gamma (IFN-gamma) could have clinical potential while many putative biomarkers showed poor association. CONCLUSIONS: Several circulating agents in peripheral blood may predict AAA size, expansion rate or rupture. Few of them have clinical potential for future use. Confirmative studies and development of multivariate models are needed, together with continuing search for new biomarkers using the discovery based sciences within proteomics and/or genomics.

Doppler ultrasound compared with strain gauge for measurement of systolic ankle blood pressure.

This study assesses measurement variation in the measurement of ankle systolic blood pressure (ABP) when measured with Doppler ultrasound and with the strain gauge method. Ninety-seven patients were included. ABP was measured with Doppler ultrasound and with the strain gauge method. The methods were compared graphically by scatterplots and analyzed by paired t test, analysis of variance, and Pitman's paired variance ratio test. ABP was measured by strain gauge in all extremities, whereas no Doppler signal was obtainable in 7 limbs (4%). There was no systematic difference in measurements between the means of the two measurements. However, a substantial difference of more than 25 mm Hg was found in 15% of limbs and more than 20 mm Hg in 20%. In the majority of patients, measurements of ABP by Doppler ultrasound and the strain gauge method give similar results, but for a minority the discrepancy is substantial.

High-risk and low-risk screening for abdominal aortic aneurysm both reduce aneurysm-related mortality. A stratified analysis from a single-centre randomised screening trial.

BACKGROUND: Cardiovascular diseases and chronic obstructive pulmonary disease (COPD) are both associated with abdominal aortic aneurysms (AAA). The aim of this study was therefore to analyse whether screening for AAA could be restricted to men with such diseases (high risk group). METHODS: Before the date of randomisation of a population screening trial of 12,639 64-73-year-old males, all discharge diagnoses from the National Patient Registry concerning AAA-related diseases were merged with the screening results on attendance, AAA prevalence, and AAA-related mortality and overall mortality. Differences in proportions were compared by Chi square tests and differences in mortality by Cox regression analyses. RESULTS: The attendance rate was 78.8% and 6.7% had an AAA in the high risk group compared to 75.8% attendance (P<0.001) and 2.9% (P<0.001) in the remaining population. Cumulatively, screening of only high risk men with would have required 72.9% (95% C.I.: 72.3-74.5%) fewer screening invitations, would have discovered 46.1% (95% C.I.: 38.9-53.4%) of the AAA cases diagnosed and prevented 46.7% (95% C.I.: 28.3-65.7%) of the AAA-related deaths. However, screening decreased AAA-related mortality both among men with and without known COPD or cardiovascular diseases: mortality ratio: 0.22 (95% C.I.: 0.08-0.65), P=0.006, and 0.24 (95% C.I: 0.09-0.63, P=0.004, respectively. CONCLUSION: High-risk population screening would prevent less than half of AAA-related deaths. Therefore, restricting screening to such high-risk groups does not seem justified, but cost effectiveness analyses are needed to reach a firm conclusion.

Preliminary ten year results from a randomised single centre mass screening trial for abdominal aortic aneurysm.

BACKGROUND: At present, several regions and countries are considering screening for abdominal aortic aneurysm (AAA). However, The Chichester Aneurysms Screening Trial has reported poor long term benefit of screening for AAA. We therefore supplement previously published data with a preliminary analysis of the ten-year mortality from AAA, based upon population-based data until 2002 (7 years) and incomplete hospital-based information on deaths until 2005 (10 years). METHODS AND MATERIAL: In 1994 we started a randomised screening trial of 12,639 64-73 year-old males; 6,306 were controls, and 6,333 were invited to an abdominal ultrasound scan at their district hospital. Information on all deaths until 15.3.2005 was obtained from the Office of Civil Registration. Information on AAA related deaths was obtained from the national registry of Causes of Deaths from 1.4.1994 to 31.12.2001, and supplemented with AAA deaths known to the Danish National Patient Registry until 15.3.2005. Operations were obtained from the Danish National Vascular Registry from 1.4.1994 to 15.3.2005. Death certificates and medical records were reviewed by two independent assessors. The analyses were based on "intention to treat" from the date of randomisation. RESULTS: The attendance rate was 76.6% and 191 (4.0%) had an AAA. The median observation time was 9.58 years. In the invited group 13 subjects were acutely operated on compared to 40 in the control group (Risk ratio: 0.32 (95% C.I. 0.17-0.60, P<0.001)), and 14 died due to AAA compared to 51 in the control group (Hazard ratio: 0.27 (95% C.I.: 0.15-0.49, P<0.001). CONCLUSION: Over ten years, screening reduced mortality from AAA by 73%, and the frequency of emergency operations by 68%.

Cost-effectiveness analysis of screening for abdominal aortic aneurysms based on five year results from a randomised hospital based mass screening trial.

BACKGROUND: The aim of this study was to estimate the cost effectiveness of screening for abdominal aortic aneurysm (AAA). MATERIAL AND METHODS: All 12,639 men born in the years 1921-1933 (aged 64-73) living in Viborg County, Denmark, were randomly allocated either to receive an invitation to abdominal ultrasound scanning for AAA or to be controls. Costs for screening and surveillance were assessed prospectively. Diagnosis Related Group (DRG) costs from 1999 were used concerning admissions with uncomplicated and complicated operations. Admissions for AAA surgery were retrospectively classified according to complications in patient records. RESULTS: Mean follow-up time was 52 months. 76.6% of invited men attended screening, and 191 (4.0%) had an AAA. As previously reported, the cumulative 5-year AAA-specific mortality in the invited group was significantly reduced by 67% compared to the control group (P = 0.003). The costs were estimated to be Euro 11.23 per scan. The costs per life-year saved were Euro 9057 (Euro 5872-20,063) after 5 years, and were expected to decrease to Euro 2708 (Euro 1758-6031) after 10 years and to Euro 1825 (Euro 1185-4063) after 15 years. CONCLUSION: Screening of 64-73 years old males in Denmark seems cost effective.

Systemic levels of cotinine and elastase, but not pulmonary function, are associated with the progression of small abdominal aortic aneurysms.

OBJECTIVE: to study whether smoking and impaired pulmonary function are associated with the expansion of abdominal aortic aneurysms (AAA). METHODS AND MATERIAL: seventy-nine men with small (3-5 cm), screen-detected AAA underwent a simple 5-step smoking history, measurement of the forced first second expiratory volume (FEV1), venepuncture and annual ultrasound scan for mean follow-up period of 3.5 years. RESULTS: all but one patient had a significantly reduced FEV1 (p<0.05, Mann-Whitney). The FEV1/expected FEV1 ratio (rFEV1) was not related to AAA expansion but was negatively correlated with P-elastase-alpha1-antitrypsin-complexes (P-Elastase). P-Elastase was positively correlated with smoking and S-cotinine. Smoking, S-cotinine, and P-elastase were positively correlated with the mean annual AAA expansion rate but not rFEV1. CONCLUSION: in general, patients with AAA have impaired pulmonary function. A simple five step smoking classification is as predictive of AAA-expansion as S-cotinine. Smoking may cause elastase secretion leading to pulmonary and aortic elastin degradation but the lack of association between AAA-expansion and rFEV1 suggest that other mechanisms are important.