Prevalence of abdominal aortic aneurysm (AAA) in first-degree relatives: detecting AAA in adult offspring of AAA patients.

BACKGROUND: First-degree relatives of patients with abdominal aortic aneurysm (AAA) may have an increased risk of developing the disease. The primary aim was to report the prevalence of AAA in adult male and female offspring of patients with AAA. The secondary aim was to explore the efficiency of a registry-based detection route, and the third aim was to report contemporary prevalence in the population. METHODS: Adult offspring of individuals with AAA and matched controls were identified through national registries. The examination included questionnaires and ultrasound examinations of the infrarenal aorta. Aortic pathology was defined as an aortic diameter ≥25 mm, AAA ≥30 mm. RESULTS: The participation rate among male and female adult offspring was 64% (350/543) and 69% (402/583), respectively. A lower participation rate was found in male and female controls (51% and 52%). No difference in prevalence of AAA was observed between male adult offspring and controls (0.9%, c.i. 0.2 to 2.3%) or in the female population (prevalence of 0.2% in adult offspring and controls). Aortic pathology and previously diagnosed AAA were detected in 5.3% (c.i. 3.3 to 8.0%) of male adult offspring and 2.3% (c.i. 1.1 to 4.2%) in controls. Aortic pathology was more prevalent among adult offspring of females with AAA. CONCLUSION: The prevalence of AAA in the general population is low, but aortic pathology is notably higher among male first-degree relatives. Increased awareness should be directed towards individuals with a possible hereditary predisposition, particularly offspring of females with AAA and older smokers. Risk factor-based targeted screening of adult offspring of patients with AAA after registry-based detection should be further explored. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT4623268.

Morphological factors associated with progression of subaneurysmal aortas.

BACKGROUND: The aim of this population-based cohort study was to assess the association between aortic morphological baseline factors in 65-year-old men with subaneurysmal aortic diameter (25-29 mm) and risk of later progression to abdominal aortic aneurysm (AAA) generally considered to be at a diameter for repair (at least 55 mm). METHODS: Men with a screening-detected subaneurysmal aorta between 2006 and 2015 in mid-Sweden were re-examined using ultrasonography after 5 and 10 years. Cut-off values for baseline subaneurysmal aortic diameter, aortic size index, aortic height index, and relative aortic diameter (with respect to proximal aorta) were analysed using receiver operating characteristic (ROC) curves, and their associations with progression to AAA diameter at least 55 mm evaluated by means of Kaplan-Meier curves and a multivariable Cox proportional hazard analysis adjusted for traditional risk factors. RESULTS: Some 941 men with a subaneurysmal aorta and median follow-up of 6.6 years were identified. The cumulative incidence of AAA diameter at least 55 mm at 10.5 years was 28.5 per cent for an aortic size index of 13.0 mm/m2 or more (representing 45.2 per cent of the population) versus 1.1 per cent for an aortic size index of less than 13.0 mm/m2 (HR 9.1, 95 per cent c.i. 3.62 to 22.85); 25.8 per cent for an aortic height index of at least 14.6 mm/m (58.0 per cent of the population) versus 2.0 per cent for an aortic height index of less than 14.6 mm/m (HR 5.2, 2.23 to 12.12); and 20.7 per cent for subaneurysmal aortic diameter 26 mm or greater (73.6 per cent of the population) versus 1.0 per cent for a diameter of less than 26 mm (HR 5.9, 1.84 to 18.95). Relative aortic diameter quotient (HR 1.2, 0.54 to 2.63) and difference (HR 1.3, 0.57 to 3.12) showed no association with development of AAA of 55 mm or greater. CONCLUSION: Baseline subaneurysmal aortic diameter, aortic size index, and aortic height index were all independently associated with progression to AAA at least 55 mm, with aortic size index as the strongest predictor, whereas relative aortic diameter was not. These morphological factors may be considered for stratification of follow-up at initial screening.

Evaluating feasibility of using national registries for identification, invitation, and ultrasound examination of persons with hereditary risk for aneurysm disease-detecting abdominal aortic aneurysms in first degree relatives (adult offspring) to AAA patients (DAAAD).

BACKGROUND: Sweden and the UK invite all 65-year-old men to a population-based ultrasound-based screening program to detect abdominal aortic aneurysms (AAA). First-degree relatives of patients with AAA are reported to have an increased risk to develop AAA, both women and men, but are not invited to screening. The "Detecting AAA in First Degree Relatives to AAA patients" (DAAAD) was designed to detect the true prevalence in adult offspring to AAA patients and to evaluate if national registries could be used for identification of index persons and their adult children with a high risk for the disease. The aim of this study is to summarize the design and methodology for this registry-based study. METHODS: The study is based on a registry-based extraction and identification of a risk group in the population with a subsequent identification of their adult offspring. The targeted risk group suffers a heredity for a potentially lethal disease, AAA (n = 750) and matched control group without heredity for AAA is also identified and invited (n = 750). The participation rate in the population-based AAA screening program for men is 75% regionally. This population is younger and have a lower prevalence. A participation rate of 65% is considered clinically adequate. For the DAAAD study, a stratified analysis of the primary outcome, prevalence, will be performed for women and men separately. Two other planned projects are based on the material: firstly, evaluation of the anxiety for disease and health-related quality of life (HRQoL) and, secondly, the cost-effectiveness of the study. DISCUSSION: In conclusion, this feasibility study will be instrumental in supporting the development of a possible new model to invite persons with high risk to develop hereditary rare diseases. To our knowledge, this is a unique, safe, and most likely to be a cost-efficient model to invite targeted risk groups for selected screening. If the study design and the results are shown to be cost-effective at the detected participation rate and prevalence, it should be further evaluated and adopted to a national screening program. The model also invites both women and men, which is unique for this specific patient group, considering that all population-based screening programs only include men. TRIAL REGISTRATION: This trial is registered at the website of Clinical Trials. CLINICALTRIALS: gov identifier, NCT4623268.

Long Term Outcome of Screen Detected Sub-Aneurysmal Aortas in 65 Year Old Men: a Single Scan After Five Years Identifies Those at Risk of Needing AAA Repair.

OBJECTIVE: The epidemiology of sub-aneurysmal aortic dilatation (SAA) 25 - 29 mm is not fully understood, and the management of SAA is debated. Lack of evidence is particularly problematic in the screening setting. This study aimed to evaluate the long term outcome of men with screen detected SAAs, focusing on progression to an abdominal aortic aneurysm (AAA), and on the AAAs reaching the threshold diameter for surgical repair. METHODS: Between 2006 and 2015, all 65 year old men with a screen detected SAA in middle Sweden were re-examined with ultrasound after five and 10 years. The primary outcomes were expansion to AAA ≥ 30 mm and progression to AAA ≥ 55 mm. Secondary outcomes were risk factors for progression, repair rate, and mortality. RESULTS: A total of 1 020 65 year old men with a SAA were identified, of whom 940 (92.2%; 95% confidence interval 91.0 - 93.8) had follow up. The Kaplan-Meier estimated incidence of AAA ≥ 30 mm development after the five year follow up (which was de facto carried out after a mean of 4.9 years) was 65.8% (61.6 - 69.4), all < 55 mm. The corresponding KM-estimated incidence after the 10 year follow up (carried out after a mean of 11.9 years) was 95.1% (90.1 - 97.4), and 29.7% (18.0 - 39.7) reached ≥ 55 mm. All 41 SAAs eventually expanding to ≥ 55 mm were ≥ 30 mm at the five year follow up. Of these, 32 had surgical repair with 100% survival, six have scheduled repairs, and three (7.3%) were unfit for repair. The KM estimated all cause mortality rates at five and 10 years were 7.0% and 17.9%, respectively, with no proven AAA related deaths. CONCLUSION: A majority of SAAs eventually progress to an AAA, of which 30% are estimated to eventually reach the threshold for repair within 10 years. A follow up policy with an ultrasound examination after five years can safely and effectively identify those SAAs at risk of developing into clinically significant AAAs needing repair and may be considered for anyone with reasonably good life expectancy.

Systematic Review and Meta-Analysis of Health Related Quality of Life and Reported Experiences in Patients With Abdominal Aortic Aneurysm Under Ultrasound Surveillance.

OBJECTIVE: Most screening and opportunistically detected abdominal aortic aneurysms (AAA) are small and kept under surveillance for several years before preventive surgery. Living with the diagnosis of an AAA may have an influence on the patient's life. Thus, it is important to study patients' experiences so that the screening process and follow up care are adapted to the patient's needs. The aim was to review systematically review the current knowledge of the effect on health related quality of life (HRQoL) and patients' experiences of living with an AAA while under surveillance. METHODS: A systematic literature review of quantitative and qualitative studies, which were quality assessed according to the GRADE system, was carried out. Pubmed, Cochrane, Embase, CINAHL, PsycINFO, and MEDLINE were searched. Narrative synthesis and meta-analysis were performed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULTS: Synthesis and meta-analyses of studies based on the Short Form-36 demonstrated that patients with an AAA consistently rated their general health (GH) lower than controls and conveyed no significant negative impact for patients with an AAA when assessed at follow up and compared with pre-screening. Synthesis and meta-analyses of HRQoL estimates encompassing mental health, anxiety, and depression demonstrated no significant differences for patients with AAA compared with controls, or within the AAA group. Qualitative studies revealed that patients with an AAA felt safe being under surveillance, and receiving a diagnosis of AAA set thoughts and feelings in motion regarding health, ageing, and mortality. Patients' lack of knowledge about the disease, its progression, and future planning can cause insecurity and worries. CONCLUSION: The current evidence does not support a negative impact on HRQoL from being under surveillance for an AAA. Qualitative data indicate that adequate patient information and professional care have the potential to reduce unnecessary worries and concerns in patients with an AAA.

The effect of ticagrelor on growth of small abdominal aortic aneurysms-a randomized controlled trial.

AIMS: To evaluate if ticagrelor, an effective platelet inhibitor without known non-responders, could inhibit growth of small abdominal aortic aneurysms (AAAs). METHODS AND RESULTS: In this multi-centre randomized controlled trial, double-blinded for ticagrelor and placebo, acetylic salicylic acid naïve patients with AAA and with a maximum aortic diameter 35-49 mm were included. The primary outcome was mean reduction in log-transformed AAA volume growth rate (%) measured with magnetic resonance imaging (MRI) at 12 months compared with baseline. Secondary outcomes include AAA-diameter growth rate and intraluminal thrombus (ILT) volume enlargement rate. A total of 144 patients from eight Swedish centres were randomized (72 in each group). MRI AAA volume increase was 9.1% for the ticagrelor group and 7.5% for the placebo group (P = 0.205) based on intention-to-treat analysis, and 8.5% vs. 7.4% in a per-protocol analysis (P = 0.372). MRI diameter change was 2.5 mm vs. 1.8 mm (P = 0.113), US diameter change 2.3 mm vs. 2.2 mm (P = 0.778), and ILT volume change 12.9% vs. 10.4% (P = 0.590). CONCLUSION: In this RCT, platelet inhibition with ticagrelor did not reduce growth of small AAAs. Whether the ILT has an important pathophysiological role for AAA growth cannot be determined based on this study due to the observed lack of thrombus modulating effect of ticagrelor. TRIAL REGISTRATION: The TicAAA trial is registered at the US National Institutes of Health (ClinicalTrials.gov) #NCT02070653.

Prevalence and natural history of and risk factors for subaneurysmal aorta among 65-year-old men.

Background: The aims of this study were to determine the prevalence of screening-detected subaneurysmal aorta (SAA), i.e. an aortic diameter of 2.5-2.9 cm, its associated risk factors, and natural history among 65-year-old men. Methods: A total of 14,620 men had their abdominal aortas screened with ultrasound and completed a health questionnaire containing information on smoking habits and medical history. They were categorized based on the aortic diameter: normal aorta (<2.5 cm; n = 14,129), SAA (2.5-2.9 cm; n = 258), and abdominal aortic aneurysm (AAA) (≥3.0 cm; n = 233). The SAA-group was rescanned after 5 years. Associated risk factors were analyzed. Results: The SAA-prevalence was 1.9% (95% confidence interval 1.7%-2.1%), with 57.0% (50.7%-63.3%) expanding to ≥3.0 cm within 5 years. Frequency of smoking, coronary artery disease, hypertension, hyperlipidemia, and claudication were significantly higher in those with SAA and AAA compared to those with normal aortic diameter. Current smoking was the strongest risk factor for SAA (odds ratio [OR] 2.8; P < 0.001) and even stronger for AAA (OR 3.6; P < 0.001). Men with SAA expanding to AAA within 5 years presented pronounced similarities to AAA at baseline. Conclusions: Men with SAA and AAA presented marked similarities in the risk factor profile. Smoking was the strongest risk factor with an incremental association with disease severity, and disease progression. This indicates that SAA and AAA may have the same pathophysiological origin and that SAA should be considered as an early stage of aneurysm formation. Further research on the cost-effectiveness and potential benefits of surveillance as well as smoking cessation and secondary cardiovascular prevention in this subgroup is warranted.

Five Year Outcomes in Men Screened for Carotid Artery Stenosis at 65 Years of Age: A Population Based Cohort Study.

OBJECTIVE: This study aimed to determine the outcome of 65 year old men five years after carotid ultrasound screening, as well as risk factors for disease progression. METHODS: All 65 year old men living in the county of Uppsala 2007-2009 were invited to an ultrasound examination of both carotid arteries and re-invited at age 70. The cohort was grouped into normal carotids, plaque without significant stenosis, moderate stenosis (50-79%), and severe stenosis (80-99%). The rate of disease progression was assessed from ultrasound data. Data on mortality, ipsilateral neurological events, risk factors, and medication were obtained from patient records and population registries. RESULTS: Among men participating in carotid screening at age 65, 3,057 were re-screened at age 70. In those with normal carotids (n = 2,318), 23 (1.0%) progressed to a moderate stenosis, and four (0.2%) to a symptomatic severe stenosis. Among those with plaque (n = 696), 25 (3.6%) progressed to moderate stenosis, and eight (1.1%) to severe stenosis, of whom four (0.6%) had symptoms. Of 31 men with 50-79% stenosis, four (12.9%) had progressed to a severe stenosis, of whom two (6.5%) developed symptoms. Five of twelve subjects (42%) with 80-99% stenosis developed symptoms. Disease regression was present among 289/692 plaque (41.7%) and 16/33 stenosis (48.4%). In multivariable analysis, smoking, coronary artery disease and hypercholesterolemia were associated with disease progression. The proportions of antiplatelet, statin, and antihypertensive treatment in the population at age 70 were 22%, 29%, and 55%, respectively. CONCLUSION: Men with plaques and moderate stenosis have a good prognosis, but in those with severe stenosis there is a high risk of neurological events.

[Misleading study in The Lancet on the outcome of the Swedish AAA screening program]. / Stor enighet om att screening för bukaortaaneurysm räddar liv.

In a recent publication in The Lancet Johansson and colleagues claim no effect on aneurysm mortality among men participating in the Swedish AAA screening program, and question its justification. The study is, however, limited by a corrupt study design and incorrect data, making the publication misleading. On the contrary, several RCTs and contemporary nationwide data with sufficient follow-up clearly show that AAA screening saves lives and is highly cost-effective. The program has so far identified about 6000 men with an AAA, of whom 1500 have been operated on to prevent rupture. Thus, more than 750 men have experienced a longer life (by a mean of 8 years) as a result of the program. Continuous evaluation of the program is important but requires a scientifically sound methodology.

Clinical Effect and Cost-Effectiveness of Screening for Asymptomatic Carotid Stenosis: A Markov Model.

OBJECTIVE/BACKGROUND: The cost-effectiveness of screening depends on the cost of screening, prevalence of asymptomatic carotid artery stenosis (ACAS), and the potential effect of medical intervention in reducing the risk of stroke. The aim of the study was to determine the threshold values for these parameters in order for screening for ACAS to be cost-effective. METHODS: The clinical effect and cost-effectiveness of ultrasound screening for ACAS with subsequent initiation of preventive therapy versus not screening was assessed in a Markov model with a lifetime perspective. Key parameters, including stroke risk, all cause mortality, and costs, were based on contemporary published data, population statistics, and data from an ongoing screening program in Uppsala county (population 300,000), Sweden. Prevalence of ACAS (2%) and the rate of best medical treatment (BMT; 40%) were based on data from a male Swedish population recently screened for ACAS. The required stroke risk reduction from BMT, incremental cost-efficiency ratio (ICER), absolute risk reduction for stroke (ARR), and number needed to screen (NNS) were calculated. RESULTS: Screening was cost-effective at an ICER of €5744 per incremental quality adjusted life year (QALY) gained. ARR was 135 per 100,000 screened, NNS was 741, and QALYs gained were 6700 per 100,000 invited. At a willingness to pay (WTP) threshold of €50,000 per QALY the minimum required stroke risk reduction from BMT was 22%. The assumed degree of stroke risk reduction was the most important determinant of cost-efficiency. CONCLUSION: A moderate (22%) reduction in the risk of stroke was required for an ACAS screening strategy to be cost-effective at a WTP of €50,000/QALY. Targeting populations with a higher prevalence of ACAS could further improve cost-efficiency.

Outcome of the Swedish Nationwide Abdominal Aortic Aneurysm Screening Program.

BACKGROUND: A general abdominal aortic aneurysm (AAA) screening program, targeting 65-year-old men, has gradually been introduced in Sweden since 2006 and reached nationwide coverage in 2015. The aim of this study was to determine the outcome of this program. METHODS: Data on the number of invited and examined men, screening-detected AAAs, AAAs operated on, and surgical outcome were retrieved from all 21 Swedish counties for the years 2006 through 2014. AAA-specific mortality data were retrieved from the Swedish Cause of Death Registry. A linear regression analysis was used to estimate the effect on AAA-specific mortality among all men ≥65 years of age for the observed time period. The long-term effects were projected by using a validated Markov model. RESULTS: Of 302 957 men aged 65 years invited, 84% attended. The prevalence of screening-detected AAA was 1.5%. After a mean of 4.5 years, 29% of patients with AAA had been operated on, with a 30-day mortality rate of 0.9% (1.3% after open repair and 0.3% after endovascular repair, P<0.001). The introduction of screening was associated with a significant reduction in AAA-specific mortality (mean, 4.0% per year of screening, P=0.020). The number needed to screen and the number needed to operate on to prevent 1 premature death were 667 and 1.5, respectively. With a total population of 9.5 million, the Swedish national AAA-screening program was predicted to annually prevent 90 premature deaths from AAA and to gain 577 quality-adjusted life-years. The incremental cost-efficiency ratio was estimated to be €7770 per quality-adjusted life-years. CONCLUSIONS: Screening 65-year-old men for AAA is an effective preventive health measure and is highly cost-effective in a contemporary setting. These findings confirm the results from earlier randomized controlled trials and model studies in a large population-based setting of the importance for future healthcare decision making.

Low prevalence of abdominal aortic aneurysm among 65-year-old Swedish men indicates a change in the epidemiology of the disease.

BACKGROUND: Screening elderly men with ultrasound is an established method to reduce mortality from ruptured abdominal aortic aneurysm (AAA; Evidence Level 1a). Such programs are being implemented and generally consist of a single scan at 65 years of age. We report the results from screening 65-year-old men for AAA in middle Sweden. METHODS AND RESULTS: All 65-year-old men (n=26,256), identified through the National Population Registry, were invited to an ultrasound examination. An AAA was defined as a maximum infrarenal aortic diameter of ≥30 mm. In total, 22 187 (85%) accepted, and 373 AAAs were detected (1.7%; 95% confidence interval, 1.5 to 1.9). With 127 previously known AAAs (repaired/under surveillance) included, the total prevalence of the disease in the population was 2.2% (95% confidence interval, 2.0 to 2.4). Self-reported smoking (odds ratio, 3.4; P<0.001), coronary artery disease (odds ratio, 2.0; P<0.001), and hypertension (odds ratio, 1.6; P=0.001) were independently associated with AAA in a multivariate logistic regression model. Thirteen percent of the entire population reported to be current smokers, one third of the frequency reported in the 1980s. The observed low prevalence of AAA was explained mainly by this change in smoking habits. CONCLUSIONS: On the basis of the observed reduced exposure to risk factors, lower-than-expected prevalence of AAA among 65-year-old men, unchanged AAA repair rate, and significantly improved longevity of the elderly population, the current generally agreed-on AAA screening model can be questioned. Important issues to address are the threshold diameter for follow-up, the possible need for rescreening at a higher age, and selective screening among smokers.