Changes in Global Mortality from Aortic Aneurysm

Abstract

Objectives:

Globally, there has been a marked increase in aortic aneurysm related deaths between 1990 and 2019. We sought to understand the underlying etiologies for this mortality trend by examining secular changes in both demographics and the prevalence of risk factors, and how these changes may vary across sociodemographic index (SDI) regions.

Methods:

We queried the Global Burden of Disease Study (GBD) for aortic aneurysm deaths from 1990–2019 overall and by age group. We identified the percentage of aortic aneurysm deaths attributable to each risk factor identified by GBD modeling (smoking, hypertension, lead exposure, and high sodium diet) and their respective changes over time. We then analyzed aneurysm mortality by SDI region.

Results:

The number of aortic aneurysm related deaths have increased from 94,968 in 1990 to 172,427 in 2019, signifying an 81.6 % increase, which greatly exceeds the 18.2% increase in all-cause mortality observed over the same time interval. Examination of age-specific mortality demonstrated that the number of aortic aneurysm deaths markedly correlated with advancing age. However, when considering rate of death rather than mortality count, overall age-standardized death rates decreased 18% from 2.72/100,000 in 1990 to 2.21/100,000 in 2019. Analysis of the specific risk factors associated with aneurysm death revealed that the percentage of deaths attributable to smoking decreased from 45.6% in 1990 to 34.6% in 2019, and deaths attributable to hypertension decreased from 38.7% to 34.7%. Globally hypertension surpassed smoking as the leading risk factor. The reported rate of deaths was consistently greater as SDI increased and this effect was most pronounced among low-middle and middle SDI regions respective (173.2% and 170.4%, respectively).

Conclusion:

Despite an overall increase in the number of aneurysm deaths, there was a decrease in the age standardized death rate, demonstrating that the observed increased number of aortic aneurysm deaths between 1990 and 2019 was primarily driven by an overall increase in the age of the global population. Fortunately, it appears that the increase in overall aneurysm related deaths has been modulated by improved risk factor modification, in particular smoking. Given the rise in aneurysm related deaths, global expansion of vascular specialty capabilities is warranted and will serve to amplify improvements in population-based aneurysm health achieved with risk factor control.

TABLE OF CONTENTS SUMMARY

Aortic aneurysm deaths increased in number between 1990 and 2019 in a global registry analysis, however mortality rate per 100,000 decreased when adjusting for age and population growth. The increase in the number of aortic aneurysm deaths was primarily driven by an overall increase in the age of the global population.

Introduction

While the focus of most vascular surgeons is directed toward the care of individual patients, global health statistics on the conditions which lie within the purview of the specialty play a crucial role in informing vascular surgeons and shaping their approach to patient care. Knowledge of the prevalence, incidence, impact on quality of life, and mortality-rates of these diseases worldwide help vascular surgeons assess the overall burden of these conditions. Understanding of the trends in these factors is critical to resource allocation, healthcare planning, prioritization of interventions, and estimation of the need for future vascular surgical resources in different countries and regions. Identifying trends in the impact of different risk factors also illuminates the opportunities for effective prevention.

The past 30 years have seen a remarkable growth in the collection and reporting of global health data. A leader in this growth and considered by many to be the gold standard for global health metrics, is the Global Burden of Diseases, Injuries and Risk Factors Study (GBD). Initiated in 1990 by the World Bank and Harvard School of Public Health, it provides a systematic scientific assessment of published, publicly available, and contributed data on disease and injury incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Sound and up-to-date evidence on trends—both progress and adverse patterns—by cause at the national level is essential to reflect effects of public health policy and medical care delivery.¹

Aortic aneurysm is one of the 369 diseases tracked by GBD. A recently published overview by Wang et al found the number of deaths globally from aortic aneurysm disease has almost doubled over the past three decades.² This increase in deaths has been observed despite advancements in screening, refinement of endovascular treatment therapies, and modification of risk factors over time.^3–5 Moreover, these increases are occurring in a period when major improvements in overall global health are taking place.¹

The primary drivers underlying the observed rise in aneurysm related deaths are not well defined, and multiple factors are likely contributing. There has been a known growth in the global population. A shift in the age distribution of the population has also been occurring, with a larger proportion of the population belonging to older age groups. This shift will impact rates of diseases that are closely tied to age, such as aortic aneurysm. Rates of disease will also be affected by increases or decreases in important risk factors or emergence of new risk factors. The degree to which each of these factors is influencing the rates in aneurysm related deaths is not well defined. Furthermore, there may be marked differences in their impact across socioeconomic regions.

Therefore, our aim was to characterize the impact of global changes in demographics and risk factors on aortic aneurysm deaths. We additionally wanted to understand how these changes varied across different sociodemographic regions.

Methods

Data Assembly

For this analysis, we utilized the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) dataset. This database is coordinated by the Institute for Health Metrics and Evaluation (IHME) and contains information regarding patient comorbidities, demographics, and disease-related mortality to provide global measures of disease burden and characteristics for 204 countries.⁶ Within the GBD database, thoracic and abdominal aortic aneurysms are grouped, and correspond to ICD-9 codes 441–441.9 and ICD-10 codes I71-I71.9.^1,7 Source metadata is available through the IHME website.⁸ The website provides an interactive results tool which we used to query specific measures and to stratify the results by risk factors and demographics of interest. We collected and analyzed these results using Microsoft Excel (Version 2208, Redmond Washington).

Mortality information is obtained from a combination of vital registration systems, verbal autopsies, and additional surveillance systems which are described on the Global Health Data Exchange website.⁶ These codes are matched to ICD codes which are then correlated with the GBD 2019 cause list.^1,2 The GBD data utilizes a Bayesian meta-regression method known as DisMod-MR 2.1 which accounts for the limitations of epidemiological data including missing data and variation in methodology between data sources.¹

Data Analysis

Our primary outcome of interest was aortic aneurysm related mortality. We used the GBD database to identify the count of aortic aneurysm deaths from 1990–2019. We identified the overall number of deaths, the death rates per 100,000 persons, and age-standardized death rates per 100,000 persons. A definition of the included statistics is presented in Supplemental Table 1. Age standardized rates within the GBD are calculated by using a non-weighted mean of 1990 and 2019 age-specific proportional distributions for all countries with a population greater than 5 million people to generate a standard population age structure.¹ For context, we additionally recorded the changes in the overall global population and life expectancy from 1990 to 2019. We grouped individuals into age categories in five-year increments from age 20 to 79, as well as one group including those less than 20 years old, and one group including those 80 years old or greater. We then calculated the change in overall global population, the number of aortic aneurysm deaths, and the aortic aneurysm death rate between 1990 and 2019 for each age group.

Risk Factor Analysis

The GBD captures data on 87 risk factors that include environmental and occupational risks, behavioral risks, and metabolic risks. We used these data to examine the percentage of aortic aneurysm deaths attributable to each of the risk factors identified by GBD modeling in 1990 and 2019. These included smoking (5 year lagged smoking prevalence), high systolic blood pressure (systolic blood pressure >140), lead exposure (>2 micrograms lead per gram of bone), and a high sodium diet (average 24 hour urine sodium >3 grams).⁹ Smoking data was collected from survey and report data available in the Global Health Data Exchange, the World Health Organization InfoBase and the International Smoking Statistics Database.⁹ Data on high systolic blood pressure was based on multi-country survey programs, national surveys, and longitudinal studies documenting either mean blood pressure or the prevalence of hypertension.⁹ Information on lead exposure was primarily collected through a review of the global literature for studies examining blood samples.⁹ Dietary data regarding sodium intake was based on nationally representative nutrition surveys, household budget surveys and United Nations Food Balance Sheets and Supply and Utilization accounts.⁹ The GBD uses comparative risk assessment modeling which creates risk-outcome pairs and weighs the contribution of each selected risk factor to aortic aneurysm death. This framework evaluates whether the risk-attributable burden is additive, multiplicative, or shared between the multiple risk factors assessed. The proportion of the burden is quantified between risk factors and this is reflected in the attributable risk value.⁹ Only risk factors identified by GBD modeling were included.

We then estimated the number of aortic aneurysm related deaths that had been averted due to changes in risk factors over time. To account for the increase in the number of deaths due to overall population increase, we calculated the change in the percentage of deaths attributable to each risk factor by subtracting the attributable risk percentage in 2019 from the percentage in 1990 and multiplying the observed number of deaths in 2019 by this difference.

Sociodemographic Index Analysis

Next, we examined the data stratified by Socio-Demographic Index (SDI) region. SDI is a tool developed by GBD researchers as a composite index of development status as correlated with health outcomes. It is a geometric mean of fertility rate under the age of 25, mean education for those aged 15 or older, and lag distributed income per capita (a regression model to predict current and past period values).¹⁰ SDI quintiles are determined based on the GBD database distribution of countries and categorized as low (e.g. Niger, Haiti), low-middle (e.g. India, Ghana), middle (e.g. China, Mexico), high-middle (e.g. Poland, Greece) and high (e.g United States, Switzerland).

Human Subject Research Protection

This study did not require institutional review board review as it involved only de-identified, publicly available data.

Results

Global Aortic Aneurysm Deaths

The number of global observed deaths attributable to aortic aneurysm was 94,698 in 1990 and 172,427 in 2019, an overall increase of 82.1%. In 1990, aortic aneurysm caused 1 of every 480 deaths but in 2019, increased to 1 of every 201 deaths. During this same period, the global population increased 44.6% (5.347 billion to 7.713 billion) while the total number of deaths grew by only 18.2%. (47.86 million to 56.53 million).

Age-Specific Aortic Aneurysm Deaths

Table 1 provides age-specific global population counts, aneurysm deaths, and age-specific death rates per 100,000 people. Age-specific death rates decreased in all age groups during the study period except for the 30–44 groups where it increased by 0.08, 0.01, and 0.01 in the 30–34, 35–39, and 40–44 age groups, respectively. There was a strong relationship between both number of deaths and death rate per 100,000 people with increasing age. As shown in Figure 1, the greatest number of deaths occurred in the 80+ age group. The 2019 death rate in the 80+ age group was over 50-fold the rate in 45–49-year age group and more than twice the rate in the 75–79 year age group. The increase in deaths in the 80+ age group alone accounted for 51.2% of the total increase in deaths.

Table 1.

Change in Global Population and Aortic Aneurysm Deaths by Age Group, 1990 and 2019 within the Global Burden of Disease Consortium

Age Group	1990: Global Population (Millions)	2019: Global Population (Millions)1	1990: Number of Aortic Aneurysm Deaths	2019: Number of Aortic Aneurysm Deaths	1990: Aortic Aneurysm Death Rate per 100,000	2019: Aortic Aneurysm Death Rate per 100,000
<20	2,273.57	2,579.27 (13.4%)	212	230 (8.5%)	0.01	0.01 (0.0%)
20–24	492.68	600.14 (21.8%)	323	377 (16.7%)	0.07	0.06 (−14.3%)
25–29	442.84	605.47 (36.7%)	504	687 (36.3%)	0.11	0.11 (0.0%)
30–34	385.63	601.73 (56.0%)	722	1,129 (56.4%)	0.08	0.19 (137.5%)
35–39	352.74	540.98 (53.4%)	1,157	1,849 (59.8%)	0.33	0.34 (3.0%)
40–44	286.29	493.44 (72.4%)	1,557	2,710 (74.1%)	0.54	0.55 (1.9%)
45–49	232.41	473.80 (103.9%)	2,164	4,118 (90.3)	0.93	0.87 (−6.5%)
50–54	212.59	436.82 (105.5%)	3,524	6,108 (73.3%)	1.66	1.40 (−15.7%)
55–59	185.42	371.01 (100.1%)	5,624	9,415 (67.4%)	3.03	2.54 (−16.2%)
60–64	160.64	312.54 (94.6%)	9,088	13,637 (50.1%)	5.66	4.36 (−23.0%)
65–69	123.49	258.58 (109.4%)	12,865	19,106 (48.5)	10.42	7.39 (−29.1%)
70–74	84.51	187.09 (121.4%)	14,560	22,743 (56.2%)	17.23	12.16 (−29.4%)
75–79	61.31	127.05 (107.2%)	17,031	25,263 (48.3%)	27.78	19.88 (−28.4%)
80+	55.72	149.53 (168.4%)	25,368	65,055 (156.4%)	45.52	43.50 (−4.4%)
All Ages	5,349.85	7,737.46 (44.6%)	94,699	172,427 (82.1%)	1.77	2.23 (26.0%)

^1.Percentage reflects change compared to number of deaths in 1990

^2.Percentage reflects change compared to death rate in 1990

Figure 1.

Aortic Aneurysm Deaths by Age Group, 1990 and 2019 within the Global Burden of Disease Consortium.

Figure 2 demonstrates the age-standardized global aneurysm death rate per 100,000 persons from 1990 to 2019, which adjusts for both changes in total population and in age distribution. In sharp contrast to the total number of deaths, the age-standardized death rate decreased by 18.2%, from 2.72/100,000 deaths in 1990 to 2.21/100,000 in 2019. This observation documents that the increase in aneurysm mortality was largely driven by the increase in both the population and age distribution, rather than by changes in the natural history of aortic aneurysm disease.

Figure 2.

Global changes in aortic aneurysm deaths between 1990 and 2019 within the Global Burden of Disease Consortium. (A) Number of deaths (B) Age standardized rate of deaths per 100,000 (C) Total global population

Aortic Aneurysm Death by Risk Factors

Over the study interval, the percentage of aortic aneurysm deaths attributable to smoking decreased from 45.6% in 1990 to 34.6% in 2019, resulting in an estimated decrease of 18,967 deaths (Table 2). The percentage of aneurysm deaths attributable to elevated blood pressure decreased to a lesser extent during this time, from 38.7% to 34.7%, resulting in an estimated decrease of 6,897 deaths. Elevated blood pressure overtook smoking as the leading risk factor. By comparison, death rates related to lead exposure and high sodium intake did not change substantially between 1990 and 2019, from 5.2% to 5.3% and 2.1% to 2.0%, respectively.

Table 2.

Impact of Risk Factors on Aortic Aneurysm Deaths, 1990–2019 within the Global Burden of Disease Consortium

Risk Factor	% Deaths Attributable to Risk Factor, 1990	% Deaths Attributable to Risk Factor, 2019	Estimated number of Deaths Averted due to Change in Attributable Risk
Current or Former Smoking	45.6%	34.6%	18,967
Elevated Systolic Blood Pressure (>110–115 mmHg)	38.7%	34.7%	6,897
Lead Exposure	5.2%	5.3%	−172
High Sodium Intake (>3 grams)	2.1%	2.0%	172

Aortic Aneurysm Death by Sociodemographic Index

Variation across SDI regions are provided in Table 3 and Figure 3 respectively. The number of deaths grew with increasing SDI. All SDI regions demonstrated an increase in deaths over the study period, but the percentage increase was greatest in the three middle SDI quintiles and smallest in the high SDI quintile. In contrast to the number of deaths, the age-standardized death rate per 100,000 people was greatest in the lowest and highest SDI regions and lower in the three middle SDI regions. While the age-standardized aneurysm death rate decreased globally during the study period, we determined that it actually increased in the three middle SDI regions.

Table 3.

Change in Deaths from Aortic Aneurysm by Socio-Demographic Index (SDI)^* Region, 1990 and 2019 within the Global Burden of Disease Consortium.

	Observed Deaths 1990	Observed Deaths 20191	Age Standardized Death Rate/100,000 People 1990	Age Standardized Death Rate/100,000 People 20192
Global	94,699	172,427 (+82.1%)	2.70	2.21 (−18.1%)
Low SDI	4,254	8,258 (+94.1%)	2.16	1.87 (−13.4%)
Low Middle SDI	7,618	20,811 (+173.2%)	1.54	1.71 (+11.0%)
Middle SDI	11,971	32,372 (+170.4%)	1.41	1.48 (+5.0%)
High Middle SDI	21,460	45,028 (+109.8%)	2.13	2.25 (+5.6%)
High SDI	49,334	65,848 (+33.5%)	4.60	3.13 (−32.0%)

^*Socio-Demographic Index is defined by lag-distributed income per capita, fertility rates among women under the age of 25, and mean education for people aged 15 or older

^1.Percentage reflects change compared to number of observed deaths in 1990

^2.Percentage reflects change compared to age standardized death rate in 1990

Figure 3.

Global changes in aortic aneurysm deaths between 1990 and 2019 by sociodemographic index (SDI)*. (A) Aortic aneurysm deaths (B) Age standardized rate of deaths per 100,000 (B) Percent of deaths attributable to smoking by SDI (C) Percent of deaths attributable to high systolic blood pressure by SDI

*Socio-Demographic Index is defined by lag-distributed income per capita, fertility rates among women under the age of 25, and mean education for people aged 15 or older

Notably, the percentage of deaths attributable to smoking fell during the study period across all regions. The largest decrease occurred in the high SDI countries. In contrast, the change in deaths attributable to high blood pressure revealed a notable decline among the high SDI regions, a moderate drop in the high-middle SDI regions and increases in the lower three SDI regions.

Discussion

This analysis of data from the GBD demonstrated that the increase in the number of global deaths from aortic aneurysm disease is largely due to an increase in the overall global population. Interestingly, this study illustrates that when normalized for population size and age distribution, the rate of aortic aneurysm related deaths has actually decreased between 1990 and 2019. We also documented that the greatest mortality burden was among older patients, and continued improvement in global longevity with expansion of the population of advanced age is likely to increase the total number of aneurysm deaths globally. Our study provides important data to guide further initiatives to reduce aneurysm deaths over time by identifying targets for further improvements in population health.

Notably, there were differences in results across different regions of the world. We observed that improvement in aortic aneurysm death rates is largely restricted to the high SDI regions. In contrast, the age-standardized death rates are increasing in the three middle SDI regions. One reason for this may be better efforts to control risk factors in the high SDI region. Smoking decreased in all regions but fell to a greater degree in the high SDI region. Smoking is known to be the most significant risk factor for aortic aneurysm development, expansion, and rupture, with a nearly eight-fold greater risk of aortic aneurysm in smokers.¹¹ While there are fewer diagnosed aneurysms in lower SDI countries, 70% of global smoking occurs there, representing a significant opportunity for risk factor modification., and thus improvements in aneurysm related mortality.¹² The differences in hypertension were even more pronounced. Hypertension decreased dramatically in the high SDI region and increased in the three middle SDI regions. These observations are aligned with studies that have demonstrated that between 2000–2010, the age-standardized prevalence of hypertension decreased 2.6% in higher SDI countries, but increased 7.7% in low and middle income countries.⁴ This represents a potential target for global health efforts to further reduce aneurysm deaths. These findings point to the importance of continued attention on the reduction of both smoking and hypertension, with particular emphasis on hypertension.

During the study period, multiple advances in aneurysm screening and treatment were introduced, which may be an additional reason for the observed discrepancies between SDI regions and observed changes over time. Advancements in endovascular treatment, individualized repair, and a growing global trend of centralization of vascular care has expanded the number of patients eligible for aneurysm repair, thereby reducing aneurysm mortality.¹¹ However, access to endovascular repair may be limited in many countries due to the high cost of devices, as well as the long term costs associated with surveillance and reintervention.¹³ The effect of aneurysm repair on overall global mortality is not known, and future efforts to discern the impact of differences in repair modality and frequency between countries could better inform optimal treatment efforts.

These data can be used to target public health initiatives towards regions most likely to benefit from attempts to reduce aortic aneurysm deaths. While we found that the number of aneurysm deaths were highest in the high SDI region, we also determined that these deaths were increasing most rapidly in the middle SDI regions. This suggests a need for continued growth in vascular surgical services globally in the coming decades, particularly in historically underserved areas. Furthermore, it would be useful to translate the improvements in aneurysm care achieved in the high SDI regions into interventions for screening and intervention that are low cost, safe and feasible in environments without sophisticated high-tech support. Risk factor modification directed at smoking cessation and blood pressure control could improve multiple aspects of cardiovascular health, including aortic aneurysm deaths, as demonstrated in the current study. We found that the aging population is at risk, and efforts may also be needed to further expand training in vascular surgery in many countries, as the number of aortic aneurysm deaths is likely to continue to rise with improvements in global longevity.

A particular strength of this analysis is the comprehensiveness of the data sets developed by the GBD. It has undertaken iterative improvement on the breadth and depth of its data and analytic efforts since its inception in the late 1980’s and is considered the gold standard source for global health metrics. It is an effort now supported by an international cohort of over 10,000 collaborating researchers. However, this study also has limitations. The GBD is based on administrative databases which may vary among countries. Aneurysm mortality is determined largely by death certificates, which may misclassify or underestimate the cause of death if an autopsy is not performed. In any database, it is estimated that deaths due to aneurysm disease may be underestimated, as it is thought approximately 5% of those who die from sudden unexplained death per year may have an undiagnosed aortic aneurysm.¹⁴ The database also lacks specificity surrounding aneurysm factors such as anatomic location, associated dissection, or incidence of rupture. Similarly, the attributable risk factors calculations are based on models built by GBD which may have an intrinsic margin of error present. The use of CT scanning as a diagnostic tool substantially increased between 1990 and 2019, leading to an increase in the discovery incidentally detected aortic aneurysms, falsely elevating the observed aneurysm mortality.^15–17 There may also be an element of improved reporting of deaths during this time, particularly in lower income countries, which could falsely increase the aneurysm mortality numbers, however some of this variation is controlled for with the GBD modeling. Despite these limitations, this dataset uniquely provides a complete global characterization of aneurysm mortality measured in over 200 countries annually and the information provides a useful benchmark for study.

Conclusion

In conclusion, improvements in longevity, and consequent growth in the elderly population appears to be a primary driver of the observed global increase in aortic aneurysm related deaths. This increase has been modulated with improved risk factor efforts, most notably, smoking. Advances in aneurysm care among high SDI countries may also be contributing to the observed mortality reduction. Current demographic trends suggest aortic aneurysm deaths will continue to grow, particularly in developing regions, and mirror regions where population growth is most pronounced. Expansion of global vascular surgery care delivery is needed, in conjunction with sustained efforts by primary care providers as well as public health professionals to modify risk factors including hypertension and smoking.

Supplementary Material

1

Supplemental Table 1. Definition of statistics included in the current analysis.

ARTICLE HIGHLIGHTS.

Type of Research:

Retrospective analysis of population health database: Global Burden of Disease

Key Findings:

Aortic aneurysm deaths increased in number between 1990 and 2019 in a global burden of disease analysis (94,968 to 172,427), however mortality rate decreased when adjusting for age and population growth (2.72/100,000 to 2,21/100,000). High blood pressure surpassed smoking as the leading risk factor for global aortic aneurysm death.

Take home Message:

There was an observed increase in the number of aortic aneurysm deaths between 1990 and 2019 which was primarily driven by an overall increase in the age of the global population.