Lower Prevalence than Expected when
Screening 70-year-old Men for Abdominal
Aortic Aneurysm
Jakob Hager, Toste Länne, Per Carlsson and Fredrik Lundgren
Linköping University Post Print
N.B.: When citing this work, cite the original article.
Original Publication:
Jakob Hager, Toste Länne, Per Carlsson and Fredrik Lundgren, Lower Prevalence than Expected when Screening 70-year-old Men for Abdominal Aortic Aneurysm, 2013, European Journal of Vascular and Endovascular Surgery, (46), 4, 453-459.
http://dx.doi.org/10.1016/j.ejvs.2013.07.014 Copyright: Elsevier
http://www.elsevier.com/
Postprint available at: Linköping University Electronic Press http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-102089
Abstract
Background: Screening 65-year old men for abdominal aortic aneurysms (AAA), is a cost-effective method to reduce the mortality from ruptured AAA. However, contemporary results show a lower than expected prevalence of AAA, thus questioning the benefit of screening. Since the prevalence increases with age, a possible way to enhance the benefit of screening might be to screen older men. Our aim was to determine the contemporary screening-detected prevalence among 70-year old men.
Methods: 5623 un-screened 70-year old men were invited to ultrasound screening. Uni- and multivariable analyses were used to assess the risk factors for AAA.
Results: The attendance rate was 84.0%. The prevalence of previously unknown AAAs was 2.3%. When adding the 64 men with an already known AAA to the screening-detected ones, the total prevalence in the population was at least 3.0%, and the previously discovered AAAs constituted 37.4% of the total prevalence.
“Ex smoker” and “Current smoker” were the most important risk factors.
Conclusions: When screening 70-year old men for AAA, the prevalence was less than half the expected, despite a high attendance rate. Smoking was the strongest risk factor. Almost 40% of the men with AAAs were already known by other means than screening.
Introduction
Ruptured abdominal aortic aneurysm (rAAA) is a common cause of death, especially among elderly men, with an overall mortality of at least 75% (1). In Sweden approximately 600 people die from this annually, comprising 1% of the total mortality among men older than 65 years of age (1). A cost-effective method of reducing the mortality from rAAA by half is by screening 65-year old men for abdominal aortic aneurysms (AAA) and surveilling those found (2). Aneurysm repair should be considered when the risk of rupture is greater than the risk of the surgical treatment, i.e. at an AAA-diameter of approximately 5.5 cm (3). Screening for AAA is now adopted around the world and is practically nationwide in e.g. England, Scotland and Sweden; and in the USA as part of the Medicare-programme (4). However, in recent studies concerning 65-year old men, a prevalence of 1.6-1.7% has been found which is only one third of the 4.9% that has previously been estimated by using a meta-analysis of studies reporting the prevalence in specifically 65-year old men (4-7).
As the prevalence of AAA seems to increase with age, there is an on-going debate whether screening of men older than 65 years might increase the efficacy of screening (5,8,9). The aims of the study were to determine the contemporary screening-detected prevalence of AAA among previously un-screened 70-year old men and to define potential risk factors and their association to AAA.
Methods
The study-population consisted of all men in Östergötland, Sweden becoming 70-years old (born 1938-40) during 2008-2010. They were previously not screened for AAA and they were identified through the National Population Registry, and with two weeks notice all, without any exclusion criteria, were invited to an ultrasound examination of the infra-renal aorta. If they were not able to attend the examination, they were urged to re-book by phone or Internet. One reminder was sent to those who did not attend or reply. The examination was free of charge but no travel expenses were reimbursed.
In order to increase the attendance rate we used a decentralized way of screening in that the examination was carried out at two of the three hospitals in the region and in addition at seven district health care centres. The examination was carried out by an experienced technician, using a portable ultrasound machine (GE Vivid i from General Electric Health Care,
Waukesha, Wisconsin, USA) with a 4C-RS probe (1.8-6.0 MHz). All together nine dedicated technicians, working in pairs, specialized in ultrasound examinations of the peripheral arterial tree, performed the scans. Fasting was not demanded and the standard position was supine. If the aorta was difficult to visualize other positions were used and/or the other technician tried to visualize the aorta. If the aorta still not could be visualized the subject was invited for a new attempt, now during fasting condition. Weight and height were also measured. Along with the invitation, an information leaflet concerning AAA was enfolded, as well as a Health Questionnaire (Appendix) to be completed prior to examination, in order to diminish recall bias. The questionnaire contained questions regarding heredity concerning AAA, smoking habits, current medication, presence or absence of the following diseases: hypertension, hyperlipidaemia, diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD), renal disease, cerebro vascular disease (CVD), claudication, coronary heart disease (CHD)
reflected as angina pectoris and/or myocardial infarction, rheumatic disease and cancer. All these data were self-reported.
An AAA was defined as the infra-renal aortic diameter being ≥ 30 mm. The aorta was
scanned with the probe in the transverse (horizontal) position and then in the sagittal (vertical) position. The greatest antero-posterior (AP) diameter of the aorta was measured according to the “leading-edge-to-leading-edge” principle (10).
From local databases men born 1938-40 with an already known AAA under surveillance were identified and excluded from the cohort, since our intention was to study men with screening-detected AAA. With aid of the Swedish Vascular Registry (Swedvasc, a nationwide register with a documented high validity) all men in our cohort who had already been treated for an AAA, were identified and excluded for the same reason (11,12).
Chi-square test with continuity correction was used for the univariate analysis, and when the validity of the chi-square test was in question (too small expected numbers in any cell of the 2x2-table) the result was checked with Fisher’s test. Univariate analyses for testing
differences in continuous variables were made with t-test. Logistic regression was used for the multivariable analysis and variables with a p-value < 0.1 from the univariate chi-square test were entered into the multivariable logistic regression (“glm” in the R-package (13)) (14). The different risk factors and medications were entered as being present or absent in the logistic regression.
The relative risk of differences in Body Mass Index (BMI) for the prevalence of AAA was calculated by exponentiation of the predicted Log Odds (from logistic regression) to Odds, by
transforming Odds to probabilities, and finally the quotient of the probabilities of the two BMIs of interest.
The expected point prevalence for 70-year old men was calculated by using data from previous studies concerning men ≥ 66 years of age by means of a multiple linear regression analysis (“lm” in the R-package (13)) (14), weighted for the number of men in each study used, Table 1 (8,15-21).
Table I. The prevalence of AAA (conventional definition) among men > 65 years of age in previous studies.
Study Mean-age (years) Numbers of patients studied Attendance rate (%) Prevalence of AAA, conventional definition (%) ADAM8 66 126196* NA 4.19 Lindholt15 67.5 4843 76.4 3.94 MASS16 69 27147 80.2 4.91 Simoni17 69 741 NA 8.77 Norman18 73 12203 63.1 7.17 Bengtsson19,20 74 375 75.2 8.27 Ljungberg21 78.6 212 NA 8 * 97% men
NA = Information not available
Calculations and statistical analyses were performed in the R-language from the R-Project for Statistical Computing (13) and Microsoft® Excel (Microsoft Corporation, Redmond,
Washington, USA) was used as a database.
Results
Altogether 5623 men became 70 years old during the years 2008-2010 and were invited to screening. The attendance rate was 84.0% and of the 4721 that attended, six men were excluded, three due to poor visibility on US-examination and three due to that they already had a known AAA under surveillance. The final screening cohort was 4715.
The mean aortic diameter was 19.7 mm. 93.4% of the men had an aortic diameter < 25 mm and 4.3% had a diameter of 25-29 mm. Eleven (10.3%) of the 107 men with a screening-detected AAA had an aneurysm of > 54 mm in diameter, thus requiring evaluation for
surgical treatment. Of the 107 AAAs, the vast majority - 93 (87%) were < 40 mm in diameter.
Thirteen men with a former known AAA did not attend screening and neither did 38 of the 48 men previously treated for an AAA/rAAA. Of the ten who had been treated and who
attended, one had developed a new AAA (32 mm in diameter), proximal to the graft. The screening detected AAA-prevalence was 2.3% (n=107). Adding the 48 men who already had been treated for an AAA/rAAA and the 16 men with non-screening detected AAA, to the screening detected AAAs, the total known prevalence was at least 3.0% (171/5623), ergo, sixty-four (37.4%) of the AAAs were already known or previously treated in this cohort.
In Table 2 the results from the univariate analysis testing for potential risk factors for AAA are shown. The most significant risk factors were “Current smoker”, “CHD” and “Renal disease”, all reaching p-values < 0.001. For those individuals who were ”Ex smokers” the prevalence of AAA was 2.5% and for those who were “Current smokers” the prevalence was 5.5%, compared to 0.65% among those who had ”Never smoked”.
Table 2. Univariate comparison between 70-year old men with or without AAA.
AAA=Abdominal Aortic Aneurysm, AA=Aortic Aneurysm, rAA=ruptured AA, CHD=Coronary Heart Disease, COPD=Chronic Obstructive Pulmonary Disease, BMI=Body Mass Index (weight/length²).
70-year old men born
1938-1940, n=4715 AAA - 2.3 % Complete registrations (%) Normal aorta - 97.7 % p-value (Chi-square test) Complete registrations (%) Risk factor
First-degree relative with AA 6.5 100 4.9 99 p=0.59 Previous rAA operation 1.9 100 0.2 99 p<0.05 Previous AA operation 1.9 100 0.6 99 p=0.27 Never smoked 11.2 100 38.2 99 p<0.001 Ex-smoker 56.1 100 50.1 99 p=0.26 Current smoker 32.7 100 11.7 99 p<0.001 Hypertension 52.9 97 44.5 95 p=0.11 Hyperlipidemia 42.9 85 31.0 88 p<0.05 Diabetes Mellitus 18.3 97 15.4 96 p=0.50 CHD 27.2 96 13.6 97 p<0.001 COPD 13.7 95 6.6 96 p<0.01 Renal disease 6.7 97 1.5 97 p<0.001 Cerebrovascular disease 16.3 97 7.3 97 p<0.01 Claudication 5.7 98 1.5 97 p<0.01 Rheumatic disease 7.7 97 5.5 97 p=0.46 Cancer 4.8 97 11.4 97 p<0.1 No medication 34.0 99 42.4 99 p=0.10 Vitamin K-antagonists 6.7 98 6.9 97 p=1.0 Heparin-group 0.0 97 0.2 97 p=1.0 Trombocyte inhibitors 43.8 98 26.4 98 p<0.001 Cardiac glucocides 1.9 97 0.9 97 p=0.57 Anti-arrhytmics 1.0 98 0.4 97 p=0.86 Vasodilators 3.8 97 3.5 97 p=1.0 Diuretics 18.3 97 14.2 97 p=0.30 Beta-receptor blockers 34.3 98 25.3 98 p<0.05 Calcium antagonists 21.1 97 14.4 97 p<0.1 Renin-angiotensin inhibitors 32.3 98 28.4 98 p=0.43 Other antihypertensives 0.0 97 0.4 97 p=1.0 Serum-lipid lowering agents 44.8 98 31.0 98 p<0.01 Corticosteroids 2.9 97 2.1 97 p=0.84 Cytotoxic agents 2.9 97 0.7 97 p<0.1 Immunosuppressive agents 0.0 97 0.4 97 p=1.0 Anti-inflammatory drugs 2.9 97 1.9 97 p=0.75 Opoids 0.9 97 1.4 97 p=1.0 Height, mean (m) 1.77 98 1.77 99 - Weight, mean (kg) 85.2 98 82.9 100 - BMI (kg/m²) 27.5 97 26.6 99 p<0.01 with t-test
An increased BMI was found among the men with an AAA, p<0.01, compared to those without (t-test). From a logistic regression analysis on BMI and AAA we found that two BMI-steps, e.g. from 25 to 27 kg/m², which in a man who is 1.77 m tall and weighs 83 kg is slightly more than 6 kg, increased the probability of having an AAA by 19.0% (relative risk).
Ten risk factors (excluding medication) had a p-value < 0.1 in the univariate analysis and these were tested in a multivariable logistic regression analysis, Table 3. Of the 4715 men in the screening cohort, 3872 had complete registrations regarding these risk factors. The two risk factors “Ex smoker” and “Current smoker” remained the strongest risk factors, OR 3.3
(95% CI 1.7-6.6) and 8.9 (95% CI 4.2-18.6) respectively, p < 0.001 for both. Also the risk factors “Renal disease”, COPD and CVD remained associated with AAA.
Table 3. Multivariable logistic regression analysis of variables associated with the presence of an AAA. Variables with a p-value <0.1 in the univariate analysis, Table 2, were included in the multivariable analysis. The number of complete observations used in the analysis is 3872 (of 4715 in the screening cohort).
Risk factor Odds ratio Confidence Interval (95%) p-value
Previous rAA-surgery 12.4 2.1-74.8 p<0.01
Never smoked --- Reference ---
Ex smoker 3.3 1.7-6.6 p<0.001 Current smoker 8.9 4.2-18.6 p<0.001 Renal disease 3.2 1.2-8.4 p<0.05 COPD 2.1 1.1-3.9 p<0.05 CVD 2.0 1.1-3.6 p<0.05 Claudication 2.0 0.7-5.6 p=0.18 CHD 1.7 1.0-3.0 p=0.053 Hyperlipidaemia 1.2 0.8-2.0 p=0.37 Cancer 0.4 0.1-1.1 p=0.079
AAA=Aortic Abdominal Aneurysm, rAA = ruptured Aortic Aneurysm, COPD = Chronic Obstructive Pulmonary Disease, CVD = Cerebro Vascular Disease, CHD = Coronary Heart Disease.
When we included BMI in the multivariable analysis, no major changes with respect to the association between AAA and the other risk factors occurred. We did not include BMI in the final multivariable analysis, since overweight in itself is not a disease, as long as BMI is < 30. Instead, quite small changes in BMI were associated with changes in risk for an AAA.
Discussion
The main finding of this screening study, comprising almost 5000 Swedish 70-year old men, was the low prevalence of AAA – 2.3%.
By using data from previous studies concerning men ≥ 66 years of age, we calculated the expected AAA-prevalence for 70-year old men (Figure 1) to 5.7% (r=0.91 and p=0.03) and the prevalence in our screening-study of 2.3% was significantly lower (p=0.014) – less than half the predicted for this age.
Figure 1. The predicted prevalence for 70-year-old men was 5.7% using data from previous studies (filled circles, from left to right: ADAM8, Lindholt15, MASS16 (below line), Simoni17 (above line), Norman18, Bengtsson19, 20 and Ljungberg21) concerning men ≥ 66 years of age (Table 1), weighted for the number of men in each study, r=0.91, p=0.003. The prevalence in this study was 2.3% (unfilled circle), thus less than half the predicted, p=0.0014.
When including men with already known AAAs, the total known prevalence was at least 3.0%, thus almost 40% of all the men with AAAs were already treated or under surveillance. However, only subjects with undetected AAAs have anything to gain from a screening program.
Smoking is the most important known risk factor for AAA and the excess prevalence for AAA associated with smoking accounts for 75% of all AAAs ≥ 4 cm (8). Smoking correlates
to increased expansion of AAA, increased risk of rupture, poorer long-term survival and quitting smoking may reduce growth rate of small AAAs (22-24).
We also found strong associations between the risk factors “Ex smoker” and AAA, and “Current smoker” and AAA, odds ratio being 3.3 and 8.9 respectively.
Approximately 20% of AAA-patients have previously been shown to have a first-degree relative with the disease (8,25-27) In our study, having a first-degree relative with AAA was not a significant pre disposing factor for AAA. The explanation for this might be that in Sweden many AAA-patients are urged to encourage their first degree relatives to have their aorta examined. This might also be one reason for the high incidental finding of AAA.
In the UK Endovascular AAA Repair 1 (EVAR 1), the Dutch Randomized Endovascular Aneurysm Repair (DREAM) and the Open Versus Endovascular Repair (OVER) trials, a positive correlation between AAA and cancer was found, and mortality due to cancer was considerably higher than AAA-related or cardiovascular mortality (28-30). The reason for the cancer-AAA correlation is probably due to the joint relation with smoking.
To our surprise we found a tendency to a lower AAA-prevalence among men with cancer, OR 0.4 (95% CI 0.1-1.1), p=0.079. One explanation might be that those individuals who are diagnosed with cancer, almost always are subjected to a CT- or MRI-scan, which means that any existing AAA is discovered and thus would be found in the group of already discovered AAA prior to screening. It is unknown whether the 64 patients with an already known AAA in our cohort, actually had a higher cancer prevalence than the study population, since we did not have the ethical permission to review case-notes of individual patients.
We found an association between increased BMI and having an AAA. Being overweight increases the risk for AAA although the effects are small compared to age, gender and smoking (26,31,32).
DM has in prior works been shown to be a protector against AAA (8,33) In our cohort of 70-year old men; the AAA prevalence was not lower among diabetics. One reason for this might be that with increasing age, the protective effect of DM decreases, as other factors
contributing to the development of AAA, e.g. atherosclerosis, become more dominant.
The lower than predicted AAA-prevalence reported in this study, is in line with the prevalence seen among 65-year old men in other contemporary studies (5,6,9,34-36).
The steep decrease in daily smoking in Sweden (Figure 2) as well as in the rest of the Western world might be one cause for the decline in AAA-prevalence, since smoking is the strongest risk factor for having an AAA (37). Thus, in countries with a similar development regarding smoking habits as in Sweden, the prevalence of AAA among 70-year old men may be expected to be as low as in this study.
Figure 2. Percentage of Swedish men, 16-84 years old, smoking on a daily basis, 1980-2005. From Statistics Sweden (SCB)37.
The use of lipid lowering agents, treatment with angiotensin-converting-enzyme (ACE) inhibitors and overall better regulation of hypertension has also been suggested as
contributors to the declining prevalence (38-40). No associations pointing in this direction were found in this cohort; on the contrary, the use of lipid-lowering agents, thrombocyte inhibitors and beta-receptor blockers, already were significantly more common among those with a screening detected AAA, indicating an already known greater cardiovascular morbidity (26). The men with an AAA also were significantly more affected by renal disease, COPD and CVD, but a bit surprising, diseases normally associated with atherosclerosis and smoking, for example claudication, CHD and hyperlipidaemia, failed to prove fully significant in our study. Most likely, the diseases associated with smoking are also associated to each other and therefore may fail to show up in the multivariable analysis as independent risk factors for AAA. Thus, if patients with smoking associated diseases, other than AAA, use lipid-lowering agents, thrombocyte inhibitors and beta-receptor blockers, this medication will also be
The prevalence of AAA among the 70year old men in this study was higher than the 1.6% -1.7% rate reported from screening 65-year-old men (4-6). This might be considered a reason to raise the age-threshold for screening. However, almost 40% of all known AAAs in the population had already been discovered, speaking against this notion (5,9). Another possible explanation for the high rate of incidentally found AAAs (besides screening of relatives and CT/MRI-scans among cancer patients, as discussed above), might be the trend, at least in Sweden, towards performing more advanced radiological examinations also in the acute setting - such as CT-scans - where most AAAs are easily seen.
We experienced a high attendance rate – 84%. The fact that we utilized a partly decentralized screening method and that the examination was free of charge might have contributed to this. Decreasing attendance rate is associated with increasing prevalence of AAA and social deprivation (41). However, despite the high attendance rate in this study, the screening detected prevalence was lower than ever reported previously for this age. Assuming that the prevalence among those individuals who did not attend screening, is the same as in the rest of this age-group, the estimated total AAA prevalence in the population would be 2.3% + 64/5623 = 3.4%.
In conclusion, when screening 4715 70-year old men in Östergötland, Sweden for AAA, we found the lowest ever reported prevalence for this age - 2.3% - less than half the predicted. When including those men who already had been treated for an AAA or were under surveillance, the total known prevalence was at least 3.0%, thus almost 40% of the AAAs were incidentally found. The most important risk factor for AAA was smoking.
The present study does not lend support to the notion that screening at a higher age than 65 years would result in detection of substantially more AAAs, since such a large part of the AAAs already are detected by other means than screening.
Acknowledgements
We would like to thank the following for contribution to this paper; Thomas Troëng M.D, Ph.D, Karlskrona for helping us retrieving data from Swedvasc and Professor John
Carstensen, Department of Epidemiology at the University Hospital in Linköping for his invaluable and constructive criticism concerning our statistical analysis.
This study was supported by grants from The Swedish Heart-Lung Foundation and King Gustav V and Queen Victoria’s foundation.
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