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Editor's Choice – Decrease in Mortality from Abdominal Aortic Aneurysms (2001 to 2015): Is it Decreasing Even Faster?

Open ArchivePublished:March 24, 2021DOI:https://doi.org/10.1016/j.ejvs.2021.02.013

      Objective

      The early twenty first century witnessed a decrease in mortality from abdominal aortic aneurysms (AAA), which was associated with variations in the prevalence of cardiovascular risk factors. This study investigated whether these trends continued into the second decade of the twenty first century.

      Methods

      Information on AAA mortality (2001 − 2015) using International Classification of Diseases codes was extracted from the World Health Organization (WHO) mortality database. Data on risk factors were extracted from the Institute of Health Metrics and Evaluation and WHO InfoBase, and data on population from the World Development Indicators database. Regression analysis of temporal trends in cardiovascular risk factors was done independently for correlations with AAA mortality trends.

      Results

      Seventeen countries across four continents met the inclusion criteria (Australasia, two; Europe, 11; North America, two; Asia, two). Male AAA mortality decreased in 13 countries (population weighted average: −2.84%), while female AAA mortality decreased in 11 countries (population weighted average: −1.64%). The decrease in AAA mortality was seen in both younger (< 65 years) and older (> 65 years) patients. The decrease in AAA mortality was more marked in the second decade of the twenty first century (2011 – 2015) compared with the first decade (2001 – 2005 and 2006 – 2010). Trends in AAA mortality positively correlated with smoking (males: p = .03X, females: p = .001) and hypertension (males: p = .001, females: p = .01X). Conversely, AAA mortality negatively correlated with obesity (males: p = .001, females: p = .001), while there was no significant correlation with diabetes.

      Conclusion

      AAA mortality has continued to decline and seems to have declined at an even faster rate in the second decade of the twenty first century, albeit with heterogeneity among countries. These variations are multifactorial in origin but further efforts targeting smoking cessation and blood pressure control will probably contribute to continued reductions in AAA mortality.

      Keywords

      The early 21st century has witnessed a global decrease in mortality from abdominal aortic aneurysms (AAA) which was associated with variations in the global prevalence of cardiovascular risk factors. This study investigates whether these trends continued into the second decade of the 21st century.

      Introduction

      Given the high mortality and morbidity associated with ruptured abdominal aortic aneurysms (AAAs), this disease has traditionally posed a heavy burden on healthcare systems. It was therefore well received when investigators started to report national declines in AAA mortality in the early twenty first century, which were attributed to a change in management of cardiovascular risk factors,
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      Aneurysm global epidemiology study: public health measures can further reduce abdominal aortic aneurysm mortality.
      as well as the introduction and expansion of endovascular aneurysm repair (EVAR).
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      Changes in abdominal aortic aneurysm epidemiology.
      ,
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      This observation was tempered by the fact that these declines were not homogenous across countries, with a few experiencing increasing mortality. Furthermore, additional studies have suggested that while overall AAA mortality may have decreased, the mortality burden may have shifted to the elderly population.
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      Changing epidemiology of abdominal aortic aneurysms in England and Wales: older and more benign?.
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      • Lookstein R.
      • et al.
      The effect of age on post-EVAR outcomes.
      It is not known if this shift in trend towards the older population is also more widespread.
      Knowledge of epidemiological trends of AAA mortality is important as it can help guide public health policies and their implementation pertaining to matters such as AAA screening practices, focused risk factor management, and early intervention strategies. For example, targeted screening may be considered in countries with higher AAA mortality and cardiovascular risk factors.
      This study aimed to determine whether AAA mortality has continued to decline in the second decade of the twenty first century together with known cardiovascular risk factors. It also aimed to investigate the rate of such a decline and whether there is any difference in AAA mortality between younger (< 65 years) and older (> 65 years) patients.

      Methods

      Mortality data

      The World Health Organization (WHO) maintains a database that tracks annual mortality by country, which is compiled based on the reports of its member states from their civil registration systems. The primary underlying cause of death is recorded according to the International Classification of Diseases, 10th Revision (ICD-10).
      To include all types of AAA in the data, ICD-10 codes I71.3 through I71.9 were used. These codes correspond to abdominal aortic aneurysms, thoraco-abdominal aortic aneurysms, and aortic aneurysms of unspecified site, both ruptured and without rupture. The age and sex associated with the mortality classifications were also acquired from this database.
      To account for differences and changes in population in statistical analysis, population data by country, gender, and year were extracted from the World Development Indicators database of the World Bank, and the population of the more developed regions of the world by age group was extracted from the World Population Prospects: 2010 Revision, Volume I, published by the United Nations Department of Economic and Social Affairs.
      For each gender, country, and year, AAA mortality was calculated as the sum of all deaths in ICD-10 codes I71.3 through I71.9 divided by the population in the age group.

      Risk factor data

      Risk factors analysed were: (1) smoking prevalence, as well as (2) cardiovascular risk factors, namely hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg), diabetes (fasting blood glucose ≥ 7.0 mmol/L) and obesity (body mass index, or BMI ≥ 30).
      Smoking prevalence was extracted from the Global Burden of Disease Study dataset, which was coordinated by the Institute of Health Metrics and Evaluation (IHME). This dataset was used because it is the only current smoking database with year to year statistics up to 2015. Other forms of tobacco intake and the consumption of tobacco derivatives were excluded in these prevalence data.
      GBD 2015 Tobacco Collaborators
      Smoking prevalence and attributable disease burden in 195 countries and territories, 1990-2015: a systematic analysis from the Global Burden of Disease Study 2015.
      Cardiovascular risk factors were obtained from Global InfoBase, a WHO maintained repository for survey information on the prevalence of risk factors for non-communicable diseases.
      Additionally, for use as a proxy for the health and socioeconomic systems of the various countries, gross domestic product (GDP) data were obtained from the International Comparison Program of the World Bank.

      Countries included

      After data were compiled from the sources above, countries were included for analysis according to the following criteria: < 30% of mortality data missing; and at least 10 annual AAA related deaths. Seventeen countries in four regions met the above inclusion criteria:
      • Australasia: Australia and New Zealand;
      • Europe: Austria, Denmark, France, Germany, Hungary, Netherlands, Norway, Romania, Spain, Sweden, and United Kingdom
      • North America: Canada and United States; and
      • Asia: Israel and Japan

      Statistical analysis

      Males and females were analysed separately. For analyses of younger vs. older patients, total adjusted (male and female) AAA deaths per year were compared between the two age groups for each country included in the analysis (adjusted deaths resulting from AAA in individuals < 65 years of age and deaths resulting from AAA in those ≥ 65 years of age).
      To interpret the relationship between mortality and risk factors, the analysis focused on annual percentage changes in the prevalence of mortality and each of the identified risk factors.
      Risks factors analysed were prevalence of smoking, obesity (measured by BMI), hypertension (measured by mean systolic blood pressure), and diabetes (measured by mean fasting blood glucose). In contrast to absolute change, percentage change accounts for differences in relative magnitude and units of measurement.
      For each risk factor with its corresponding country, the percentage change of its prevalence was plotted on a time graph. Next, the cross section of the average annual percentage changes in the prevalence of mortality and risk factor for each country and the corresponding linear regression line of the annual percentage changes in the prevalence of mortality and risk factor, both weighted by country population, were plotted graphically. Analysis of percentage change accounts for the probable non-linear relationship between mortality and risk factor. Weighting by population accounts for the relative size of the various countries.
      In addition, a bivariable regression of mortality prevalence on the prevalence of the risk factor was estimated. The models were fitted by ordinary least squares with fixed effects for countries and robust standard errors using Stata/MP14 (StataCorp, College Station, TX, USA). The country fixed effects account for differences among countries such as healthcare systems and reporting standards that did not vary within the period of study. Statistical significance was assessed with t statistics.

      Results

      Abdominal aortic aneurysm mortality rates

      Between 2001 and 2015, 13 of the 17 countries analysed experienced declines in male AAA mortality. The countries with the largest average annual decreases were the United States (−5.24%), the United Kingdom (−4.53%), and the Netherlands (−4.27%). The United Kingdom and the United States were also notable for being the only countries with a decrease in mortality for every recorded year. The four countries that had overall increasing male AAA mortality were Hungary, Israel, Japan, and Romania, of which Hungary had the largest increase (+4.71%) (Fig. 1).
      Figure 1
      Figure 1Mean annual change in abdominal aortic aneurysm related mortality in (A) males and (B) females. USA = United States of America; AUS = Australia; GBR = United Kingdom; NLD = Netherlands; SWE = Sweden; FRA = France; NOR = Norway; CAN = Canada; NZL = New Zealand; DEU = Germany; ESP = Spain; AUT = Austria; DNK = Denmark; JPN = Japan; ROU = Romania; ISR=– Israel; HUN = Hungary.
      During the same time period, 11 countries experienced declines in female AAA mortality. The countries with the largest average annual drops were the United Kingdom (−4.65%), the United States (−4.04%), and Australia (−3.02%). No country experienced declines in female mortality every year. Austria, Denmark, Hungary, Romania, Japan, and Spain experienced an increase in female AAA mortality (Fig. 1).
      Across the countries analysed, the raw average change in male AAA mortality per country per year was −1.79%; which corresponded to −2.84% when countries were weighted by population per year. For females, the country average change was −0.74%, and the population weighted change was −1.64%. Of note, Israel experienced an increase in male mortality but a decrease in female mortality.

      Age stratification

      The proportions of people with AAA related mortality aged < 65 years and > 65 years varied significantly between countries. There was no significant difference in mortality between younger and older patients, with both age groups showing a declining trend (Fig. 2). Similar results were also demonstrated when using 75 years as cut off between younger and older patients (data not shown).
      Figure 2
      Figure 2Proportion of abdominal aortic aneurysm (AAA) related mortality per 1000 persons below and over age 65, by country, from 2001 to 2015. USA = United States of America; AUS = Australia; GBR = United Kingdom; NLD = Netherlands; SWE = Sweden; FRA = France; NOR = Norway; CAN = Canada; NZL = New Zealand; DEU = Germany; ESP = Spain; AUT = Austria; DNK = Denmark; JPN = Japan; ROU = Romania; ISR=– Israel; HUN = Hungary.

      Smoking

      The global prevalence of smoking has been on the decline; the male population weighted prevalence decreased from 27.3% in 2001 to 19.9% in 2015, with each year having a lower prevalence than the preceding one. The same trend was observed in females, with a decrease from 18.1% to 14.3%. In the male population, Japan (−1.09%), Denmark (−0.93%), and Norway (−0.64%) demonstrated the most rapid average annual declines, while Austria (−0.07%) and Israel (−0.14%) showed the slowest annual declines. Correspondingly in females, Denmark (−0.65%) and Norway (−0.49%) had the largest declines, while Romania (−0.01%) and Israel (−0.07%) had the smallest (Fig. 3).
      Figure 3
      Figure 3Change in abdominal aortic aneurysm (AAA) mortality against smoking prevalence in (A) males, and (B) females across countries from 2001 to 2015. USA = United States of America; AUS = Australia; GBR = United Kingdom; NLD = Netherlands; SWE = Sweden; FRA = France; NOR = Norway; CAN = Canada; NZL = New Zealand; DEU = Germany; ESP = Spain; AUT = Austria; DNK = Denmark; JPN = Japan; ROU = Romania; ISR=– Israel; HUN = Hungary.
      AAA related mortality was strongly correlated with smoking prevalence in both the male and female populations. Specifically, for each percentage point decrease in smoking, male AAA mortality decreased by 0.027%, (p = .03X) compared with 0.019% in females (p = .001) (Fig. 3).

      Hypertension

      Decreases in the prevalence of hypertension were observed in every country. In males, the population weighted prevalence decreased from 25.5% to 20.1%, and in females from 17.6% to 12.9%. In males, the steepest declines were seen in Germany (−0.70%) and the United Kingdom (−0.65%) while the slowest declines were in Romania (−0.12%), and the United States (−0.14%) (Fig. 4).
      Figure 4
      Figure 4Change in abdominal aortic aneurysm (AAA) mortality against hypertension prevalence in (A) males, and (B) females across countries from 2001 to 2015. USA = United States of America; AUS = Australia; GBR = United Kingdom; NLD = Netherlands; SWE = Sweden; FRA = France; NOR = Norway; CAN = Canada; NZL = New Zealand; DEU = Germany; ESP = Spain; AUT = Austria; DNK = Denmark; JPN = Japan; ROU = Romania; ISR=– Israel; HUN = Hungary.
      There was a significant positive correlation between hypertension and AAA related mortality in both sexes. For each percentage point decrease in hypertension, male AAA related mortality decreased by 0.00041%, (p = .001); while female AAA related mortality decreased by 0.00015%. (p = .01X) (Fig. 4). Sensitivity analysis performed without the USA demonstrated fidelity: both male and female AAA related mortality were still significantly positively correlated with hypertension (males: 0.00040%, p = .001; females: 0.00014%, p = .01X).

      Obesity

      Obesity prevalence increased in all countries analysed. From 2001 to 2015, the population weighted prevalence increased from 17.4% to 25.3% in males, and from 19.0% to 25.3% in females. For both the male and female populations, the largest and smallest annual increases were observed in the United States (male: 0.71%, female: 0.63%) and Japan (male: 0.18%, female: 0.09%), respectively. The United States and Japan were also the countries with the highest (male: 34.7%, female: 36.4%) and lowest prevalence of obesity (male: 4.6%, female: 3.6%) in 2015 (Fig. 5).
      Figure 5
      Figure 5Change in abdominal aortic aneurysm (AAA) mortality against obesity prevalence in (A) males, and (B) females across countries from 2001 to 2015. USA = United States of America; AUS = Australia; GBR = United Kingdom; NLD = Netherlands; SWE = Sweden; FRA = France; NOR = Norway; CAN = Canada; NZL = New Zealand; DEU = Germany; ESP = Spain; AUT = Austria; DNK = Denmark; JPN = Japan; ROU = Romania; ISR = Israel; HUN = Hungary.
      There was a significant negative correlation between obesity and AAA related mortality; for each percentage point increase in obesity, male AAA related mortality decreased by 0.00039%, (p = .001); while female AAA related mortality decreased by 0.00021% (p = .001) (Fig. 5).

      Diabetes

      Overall, the population weighted prevalence of diabetes increased in males from 6.81% to 7.56%, and in females from 5.28% to 5.38%. However, these trends varied significantly between sexes as well as countries. Of the 17 countries analysed, 16 experienced increases in males, compared with only six in females.
      AAA mortality did decrease with decreased diabetes prevalence among both males and females, although neither of these correlations were statistically significant. To verify this finding, a multiple regression was run including the prevalences of diabetes and obesity. This showed that increased male diabetes prevalence was associated with decreased AAA mortality (p = .01X), although female diabetes prevalence remained not statistically significant (p = .27).

      Gross domestic product

      When analysing GDP, the United States had by far and away the greatest increases in GDP, with over double the rates of Japan and Germany, which completed the top three countries for GDP growth. However, there was no statistically significant correlation between GDP growth and AAA mortality (males p = .18, females p = .27); this finding can be attributed to the GDP of every studied country increasing over the specified time period and to country fixed effects.

      Rates of change of mortality vs. statistically significant risk factors

      Over the time period analysed, the rate of AAA mortality and risk factor change was tabulated by sex (Table 1, Table 2). Only years that included all 17 countries were used to analyse three separate time periods: 2001 – 2005, 2006 – 2010, and 2011 – 2015.
      Table 1Rate of mortality and positive, statistically significant risk factor change over time in males with abdominal aortic aneurysm
      Time period
      2001–20052006–20102011–2015
      Mortality−0.13−2.39−3.42
      Smoking−2.27−2.33−1.44
      Hypertension−2.20−2.41−2.36
      Data are presented as % per year.
      Table 2Rate of mortality and positive, statistically significant risk factor change over time in females with abdominal aortic aneurysm
      Time period
      2001–20052006–20102006–2010
      Mortality−0.38−0.70−2.61
      Smoking−1.94−2.17−1.18
      Hypertension−1.64−1.90−2.01
      Data are presented as % per year.
      The rate of decline in AAA mortality increased in both the male and female populations; this was in line with the rates of decline in hypertension prevalence. On the other hand, rates of decline in smoking prevalence, peaked in the 2006 – 2010 period for both males (−2.33%) and females (−2.17%).

      Discussion

      This study represents the largest population based analysis of AAA mortality to date and it confirmed that AAA mortality continued to decline into the second decade of the twenty first century, in association with reductions in smoking and hypertension. These rates of decline in AAA mortality seem to be accelerating for both males and females when analysed across three time periods, namely 2001 – 2005, 2006 – 2010, and 2011 – 2015. This study also confirmed that AAA related mortality has declined regardless of age group, with those aged > 65 years showing a similar trend to those aged < 65 years, with no evidence to suggest a shift in AAA burden to the older age group.
      The analyses from this study yielded optimistic results. The data indicated that AAA mortality is not only declining, but also doing so at a faster rate than ever, correlating with the reduction in cardiovascular risk factors. Male mortality rates have decreased at a rate from −0.13% in 2001 – 2005 to −3.42% in 2011 – 2015; similar trends were demonstrated in females from −0.38% in 2001 – 2005 to −2.61% in 2011 – 2015, albeit by a smaller margin. Whether this AAA mortality disadvantage in females is a true discrepancy remains difficult to ascertain, although it is known that women have, in general, worse post-operative AAA repair outcomes.
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      The present analyses showed a statistically significant correlation between declines in AAA mortality and smoking prevalence. Attempts have been made to establish the relationship between smoking and the pathogenesis of AAA by the use of enhanced animal models and have shed light on the possible lasting alterations in vascular smooth muscle cell and inflammatory cell function.
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      Smoking cessation measures should be encouraged given its association with reduced AAA incidence and mortality, as well as cardiovascular and respiratory disease. In the past two decades, overall global tobacco use has fallen, from 1.397 billion in 2000 to 1.337 billion in 2018, according to a WHO global report on trends in prevalence of tobacco use. Yet, this still falls short of the global target to cut tobacco use by 30% by 2025.
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      Furthermore, any satisfaction derived from the abovementioned decreases in tobacco smoking should be tempered by vaping tobacco use rapidly increasing worldwide, and the impact of this method of tobacco consumption on AAA mortality is as yet unknown.
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      Nevertheless, this study showed a decline in rate of decrease of smoking in years 2011 – 2015 from 2006 – 2010, which reinforces the need to sustain smoking reduction strategies, maintain desirable trajectories for tobacco control, and achieve global convergence towards elimination of tobacco use.
      The present analysis showed a weakly positive but statistically significant association between reduction of AAA mortality and hypertension. The influence of elevated blood pressure on AAA is substantially less than its influence on other cardiovascular diseases, and it is estimated that the abdominal aortic aneurysm is only 1.1 times more common in patients with hypertension than in those with normal blood pressure.
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      Existing literature regarding the role of hypertension in AAA is also inconclusive, especially with regard to any association hypertension may have on incidence of AAA. However, it more consistently supports an association between hypertension and AAA rupture compared with AAA expansion.
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      Of note, the latest analysis of the Million Veteran Program has demonstrated that diastolic hypertension, as opposed to systolic hypertension, is of greater significance in the pathogenesis of AAA,
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      although recent changes to the definition of systolic hypertension (a decrease from 140 mmHg to 130 mmHg) may change these findings and will be worth studying moving forward.
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      This study showed a significant inverse relationship between obesity and AAA mortality, using BMI as a surrogate measure for obesity. This is similar to findings from a meta-analysis by Sweeting et al., which reported a non-significant inverse association between BMI and growth rate of small AAAs.
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      However, the relationship between obesity and AAA mortality remains unclear, and data should be interpreted with caution. For instance, some studies have shown that only abdominal adiposity (measured by waist circumference) and not total adiposity (measured by BMI) was associated with increased risk of AAA
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      A study with alternative anthropometric data measurements may therefore yield different conclusions.
      The present study demonstrated a trend towards an inverse relationship between diabetes mellitus and AAA mortality but this was not statistically significant. When controlling for obesity, there was a statistically significant signal that showed a protective effect of diabetes against AAA mortality among males, which suggests that the association between reduction in AAA mortality and obesity cannot be explained solely by diabetes, and vice versa. This signal, however, was not robust as it did not carry over to the female population. Previous studies have also shown a negative association and there is evidence demonstrating a paradoxically beneficial effect of diabetes against AAA expansion and rupture.
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      Ultimately, the relationship between diabetes, obesity, and AAA outcomes would be better elucidated by large scale, longitudinal population based studies.
      There were several limitations to this study. First, while the epidemiological study design allowed for large scale comparisons across countries, relationships may not be generalisable to the individual. Moreover, data collection disparities between countries may affect interpretation of mortality and risk factor data. Second, AAA mortality rates may be under reported depending on whether an autopsy was performed, and rates over reported if a particular country had a screening programme for AAA. Thirdly, mortality rates are also dependent on other factors, including the incidence of rupture, out of hospital rupture, proportion of patients who went for elective or emergency repair, as well as peri-operative mortality. These may be significant confounding factors in analysing risk factor relationships with mortality, for which operative data would assist in clarifying. Finally, despite the original intent of this study, the resulting pool of included countries sorely lacked representation from South American, African, and Asian countries. Notably, China and India, the two most populous countries, were among countries with < 50% of mortality data required and as such could not be included in the analysis. Of non-Western countries, only Israel and Japan met the inclusion criteria for this study. This is significant because white people have been shown to have a 10 fold higher incidence of AAA than Asian people,
      • Salem M.K.
      • Rayt H.S.
      • Hussey G.
      • Rafelt S.
      • Nelson C.P.
      • Sayers R.D.
      • et al.
      Should Asian men be included in abdominal aortic aneurysm screening programmes?.
      and whether their mortality and risk profiles would be representative of non-white populations as well remains to be proven.

      Conclusion

      This study identified pertinent trends of decreasing AAA related mortality going into the second decade of the twenty first century. Reduction in smoking and cardiovascular risk factors may be contributing factors to the reduction in AAA related mortality. A greater understanding of the epidemiology and risk factors at a population level will be helpful in informing future AAA related healthcare policy strategies.

      Conflict of interest

      None.

      Funding

      None.

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      Linked Article

      • Are We There Yet? The Race To Eliminate Aortic Aneurysm-Related Mortality
        European Journal of Vascular and Endovascular SurgeryVol. 61Issue 6
        • Preview
          Dr. Png and colleagues have nicely demonstrated a down-trend in abdominal aortic aneurysm (AAA) mortality in 17 countries over a 15 year time period.1 Despite transformative advances in the treatment of AAA over the last three decades, AAA-related mortality remains significant in multiple countries. As a result of many factors, mortality continues to decline slowly,1 but may be accelerating according to these authors.
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