Researchers analyzed mortality data from the CDC WONDER database regarding deaths related to NSAH among young adults aged 15 to 64 years old between 1999 and 2022. The Multiple Cause of Death database from the CDC WONDER site was utilized to analyze all deaths associated with this specific disease state. The International Classification of Diseases (ICD), 10^th Revision, Clinical Modification codes were utilized to separate out data relevant to this study. To capture all data regarding NSAH, the ICD-10 code I60 was utilized, which includes both aneurysmal and non-aneurysmal causes of NSAH.

Data was extracted from two distinct time periods, 1999 to 2020 and 2020 to 2022, and then combined for analysis. Data regarding NSAH-related deaths was analyzed across different sexes races, regions, states, rural vs. urban settings, and age. The relevant data extracted included number of deaths, crude mortality rates, and age-adjusted mortality rates (AAMR) with 95% confidence intervals (CI) for each stratifying variable. The CDC WONDER database contains public information that is anonymized; as such, this study was exempt from institutional review board (IRB) approval.

The study population included five age groups in 10-year intervals from 15–24, 25–34, 35–44, 45–54, and 55–64 years old. Sexes included male or female. Race and ethnicity groups included White, Black or African American, Asian or Pacific Islander, and Hispanic or Latino. Data was stratified into rural and urban classifications, based on the National Center for Health Statistics Urban–Rural Classification Scheme as used by the CDC WONDER database (13). Data was also stratified by state, as well as by United States census regions (Northeast, Midwest, South, and West), as defined by the Census Bureau definitions utilized by the CDC WONDER database. States included in each region can be seen in Table 1. Regional data as well as rural vs. urban data were only analyzed between 1999 and 2020 because data provided for 2020–2022 was marked as provisional on the CDC WONDER database.

AAMR as well as average annual percentage change (AAPC) were analyzed throughout the study period among each stratification. Data were compiled and organized via Microsoft Excel, where the article’s primary figures were created. Beyond initial charts and graphs, Joinpoint regression was conducted to further analyze this data. This study utilized the Joinpoint Regression Program (Joinpoint version 4.9.0.0 available via the National Cancer Institute in Bethesda, Maryland) to determine both overall mortality trends as well as those specified to stratified variables (14). Joinpoint regression allowed researchers to identify whether significant changes in mortality occurred throughout the study period and if so, when those changes occurred (14). The Monte Carlo permutation test was also utilized to calculate annual percent changes (APC) for each AAMR calculated, all reported with 95% CIs (14). Average values of the APCs were calculated as AAPCs and reported to further highlight mortality trends throughout the study period. Differences in mortality and trends were analyzed utilizing 2-tailed t-tests with statistical significance set at p ≤ 0.05. Statistically significant data is represented with an asterisk ‘*’ throughout this paper.

Between 1999 and 2022 there were 85,930 deaths related to NSAH. Annual total deaths, as well as annual stratification of mortality by sex as well as by race/ethnicity can be seen in Table 2.

Overall, the NSAH-related AAMR decreased between 1999 and 2022 (AAPC: −1.81*, 95% CI: −2.12 to −1.55) (Figure 1; Supplementary Figure 1; Supplementary Table 1). Overall AAMR decreased from 2.33 in 1999 to 1.36 in 2014 (APC: −3.53*, 95% CI: −4.08 to −3.15), indicating a significant reduction in mortality. AAMR then increased insignificantly to 1.45 in 2022 as a tentative observation (APC: 1.50, 95% CI: 0.39 to 3.16) but still represented a downward trend throughout the study period (Figure 1; Supplementary Table 1). These short-term fluctuations require further investigation, but overall, long-term decline in NSAH-related mortality occurred between 1999 and 2022 in the US.

Females had consistently higher AAMRs than males throughout the study period (Supplementary Figure 1). However, females did have a larger decrease in overall mortality than men between 1999 and 2022, respectively (AAPC −2.25*, −1.36* respectively) (Supplementary Table 1; Figure 2). Men’s AAMR decreased significantly from 1.9 in 1999 to 1.21 in 2013 (APC: −2.94*, 95% CI: −4.44 to −2.20), but proceeded to increase to 1.25 in 2022, a brief temporal trend noted in this study’s results (APC: 1.16, 95% CI: −0.31 to 5.09) (Supplementary Table 1; Figure 2). Females experienced a decline in AAMR from 1999 to 2014, with the value dropping from 2.73 to 1.49 (APC: −4.02*, 95% CI: −4.52 to −3.61) (Supplementary Table 1; Figure 2). Female AAMR proceeded to increase to 1.64 in 2022, however, which is a tentative observation that must be further evaluated (APC: 1.15, 95% CI: −0.09 to 3.14) (Supplementary Table 1; Figure 2).

Throughout the study, there was wide variation in NSAH-related AAMR across different racial groups, with Black or African American patients and American Indian or Alaskan Native patients having the highest AAMRs overall (Supplementary Figure 2).

American Indian or Alaska Native patients experienced a decrease in AAMR from 2.43 in 1999 to 1.63 in 2018 (APC: −2.03*, 95% CI: −8.42 to −0.47), but a short-term rise to 2.63 in 2022 (APC: 12.16, 95% CI: −0.23 to 40.73) (Supplementary Table 2; Figure 3). This represents an overall increase in NSAH-related AAMR among Native American patients between 1999 and 2022, although shorter term observations must be further analyzed (AAPC: 0.30, 95% CI: −1.72 to 1.79) (Supplementary Table 2; Figure 3).

Asian or Pacific Islander NSAH patients experienced a decrease in AAMR from 2.26 in 1999 to 1.36 in 2014 (APC: −2.67*, 95% CI: −7.33 to −1.22) but a subsequent increase to 1.36 in 2022 (APC: 0.15, 95% CI: −1.86 to 7.60) (Supplementary Table 2; Figure 3). This represents an overall decrease in NSAH-related AAMR among Asian or Pacific Islander patients between 1999 and 2022, with some short-interval fluctuations throughout the study period (AAPC: −1.69*, 95% CI: −2.40 to −1.01) (Supplementary Table 2; Figure 3).

Black or African American NSAH patients experienced a decrease in AAMR from 4.01 in 1999 to 1.95 in 2015 (APC: −4.40*, 95% CI: −5.03 to −3.92) but a subsequent increase to 2.16 in 2022 (APC: 2.05*, 95% CI: 0.36 to 5.30) (Supplementary Table 2; Figure 3). This represents an overall decrease in NSAH-related AAMR among Black or African American patients between 1999 and 2022, with short-term fluctuations that require further analysis (AAPC: −2.48*, 95% CI: −2.86 to −2.14) (Supplementary Table 2; Figure 3).

White patients experienced a decrease in AAMR from 2.02 in 1999 to 1.21 in 2013 (APC: −3.71*, 95% CI: −4.33 to −3.23), followed by little change in AAMR at 1.20 in 2022 (APC: 0.52, 95% CI: −0.50 to 2.34) (Supplementary Table 2; Figure 3). This represents an overall decrease in NSAH-related AAMR among White patients between 1999 and 2022, with outside factors potentially contributing to the tentative trends found within the study period (AAPC: −2.07*, 95% CI: −2.38 to −1.79) (Supplementary Table 2; Figure 3).

Hispanic or Latino NSAH patients experienced a short-term decrease in AAMR from 2.60 in 1999 to 1.52 in 2015 (APC: −3.29*, 95% CI: −3.81 to −2.86) followed by a short-term increase to 1.67 in 2022 (APC: 2.30*, 95% CI: 1.01 to 4.31) (Supplementary Table 2; Figure 3). This represents an overall decrease in NSAH-related AAMR among Hispanic or Latino patients between 1999 and 2022, with short-term fluctuations throughout the study period (AAPC: −1.62*, 95% CI: −1.91 to −1.33) (Supplementary Table 2; Figure 3).

Through 1999 to 2020, deaths caused by NSAH in the young-adult population decreased significantly in all regions, with AAPCs of −2.67 (CI 95%: −3.11, −2.24) in Northeast, −2.64 (CI 95%: −3.13, −2.25) in Midwest, −1.9649 (CI 95%: −2.51, −1.54) in South, −1.9426 (CI 95%: −2.45, −1.43) in West, respectively, (Figure 4; Supplementary Figure 3; Supplementary Table 3).

In 1999, the highest AAMR was observed in the South (2.53 deaths per 100,000 people), while the lowest was in the Northeast (2.06 deaths per 100,000 people) (Supplementary Table 3). The Northeast region AAMR tentatively decreased from 2.06 in 1999 to 1.31 in 2012 (APC: −3.79*, 95% CI: −5.01 to −3.19) and short-term decreased again to 1.28 in 2020 (APC: −0.82*, 95% CI: −2.21 to 2.89) (Figure 4; Supplementary Table 3). The Northeast saw a significant decrease in AAMR from 1999 to 2012, but the short-term fluctuations leveled off between 2012 and 2020 (Figure 4; Supplementary Table 3).

The Midwest region AAMR temporarily decreased from 2.29 in 1999 to 1.35 in 2013 (APC: −3.75*, 95% CI: −5.17 to −3.22) and decreased in the short-term again to 1.40 in 2020 (APC: −0.38*, 95% CI: −2.20 to 5.27) (Figure 4; Supplementary Table 3). These fluctuations represented an overall decrease throughout the study period (Figure 4; Supplementary Table 3).

The South region AAMR decreased from 2.53 in 1999 to 1.29 in 2015 (APC: −3.5777*, 95% CI: −4.44 to −3.03) and then increased to 1.68 in 2020 (APC: 3.38*, 95% CI: 0.15 to 12.22) (Figure 4; Supplementary Table 3). These represent tentative observations in the data, and represent an overall decrease in NSAH-related mortality (Figure 4; Supplementary Table 3).

The West region AAMR tentatively decreased from 2.23 in 1999 to 1.45 in 2011 (APC: −3.43*, 95% CI: −5.37 to −2.54), and saw a short-term increase to 1.51 in 2020 (APC: 0.07*, 95% CI: −1.26 to 4.13) (Figure 4; Supplementary Table 3). The West, similar to the Northeast and saw an overall decrease in NSAH-related mortality, despite short-term fluctuations throughout the study period (Figure 4; Supplementary Table 3).

From 1999 to 2022, most of U.S. states experienced a significant decline in AAMRs from NSAH. States like California, Arizona, and Alabama demonstrated some of the most dramatic improvements. For instance, California’s AAMR dropped from 2.37 per 100,000 in 1999 to 0.08 in 2022, while Arizona went from 2.17 to 0.17, and Alabama from 2.88 to 0.22. These represent sustained and substantial public health gains.

Similarly, states like Georgia, Michigan, and Florida also showed consistent downward trends over the 23-year period. Florida’s AAMR, for example, decreased from 2.46 in 1999 to 0.11 in 2022, despite a temporary uptick to 2.01 in 2020.

However, not all states followed a steady path. Several, such as Hawaii, Indiana, and Mississippi, saw intermediate spikes in AAMRs. These changes represent tentative observations, those of which need further investigation to establish as true trends. Hawaii’s rate rose from 2.53 in 1999 to 3.78 in 2020 before plunging to just 0.06 in 2022. A similar trend occurred in Indiana, where AAMR rose from 1.49 to 2.14 between 1999 and 2020, then fell sharply to 0.17 by 2022. Several states—including Alaska, Montana, Rhode Island, South Dakota, North Dakota, District of Columbia and Wyoming—had missing or unreliable data in multiple years. This limits the ability to evaluate trends in those locations with confidence. State-level data in NSAH-related mortality is represented in Supplementary Figures 4, 5.

The AAMR for NSAH showed a general decline in both urban and rural areas from 1999 to 2020 (Supplementary Figure 6).

In urban areas, the NSAH-related AAMR temporarily decreased from 2.35 deaths per 100,000 people in 1999 to 1.37 in 2013 (APC: −3.78*, 95% CI: −4.44 to −3.30), and then increased in the short term to 1.46 in 2020 (APC: 0.39, 95% CI: −1.11 to 3.83) (Supplementary Table 4; Figure 5). Similarly, rural areas experienced an initial tentative decline in NSAH-related AAMR from 2.22 in 1999 to 1.53 in 2012 (APC: -2.94, 95% CI: −6.45 to 1.15) (Supplementary Table 4; Figure 5). Rural areas proceeded to see a subsequent short-term decrease in NSAH-related AAMR to 1.47 in 2018 (APC: -0.59, 95% CI: −5.33 to 1.44) but then saw a tentative increase to 1.82 in 2020 (APC: 10.48*, 95% CI: 1.46 to 16.81) (Supplementary Table 4; Figure 5).

The crude mortality rate for NSAH showed a declining trend across all age groups from 1999 to 2022, though the degree of reduction varied by age (Supplementary Figure 7). The 55–64 age group consistently had the highest crude mortality rates throughout the study period (Supplementary Figure 7).

In the 15–24 age group, the crude mortality rate remained relatively low throughout the study period but declined from 0.2 per 100,000 in 1999 to 0.09 in 2022 (APC: −2.01*, 95% CI: −3.06 to −1.06) (Figure 6; Supplementary Table 5).

For individuals aged 25–34 years, the crude mortality rate initially decreased from 0.68 in 1999 to 0.45 in 2014 (APC: −2.83*, 95% CI: −3.97 to −2.20) and then increased slightly in the short term to 0.46 in 2022 (APC: 1.33, 95% CI: −0.30 to 5.15) (Figure 6; Supplementary Table 5). Among those 35–44 years old, the crude mortality rate tentatively decreased from 2.38 in 1999 to 1.23 in 2013 (APC: −4.37*, 95% CI: −5.46 to −3.67), but then increased slightly in the short term to 1.3 in 2022 (APC: 0.49, 95% CI: −1.04 to 3.92) (Figure 6; Supplementary Table 5).

In the 45–54 age group, the crude mortality rate tentatively declined from 4.02 in 1999 to 2.37 in 2015 (APC: −3.23*, 95% CI: −4.15 to −2.72), then saw a short-term increase to 2.48 in 2022 (APC: 1.27, 95% CI: −0.79 to 8.04) (Figure 6; Supplementary Table 5). For the 55–64 age group, the crude mortality rate tentatively declined from 5.48 in 1999 to 3.46 in 2012 (APC: −3.65*, 95% CI: −4.47 to −3.00), but then significantly increased to 3.69 in 2022 (APC: 1.13*, 95% CI: 0.27 to 2.50) (Figure 6; Supplementary Table 5). These represent short-term fluctuations, but the overall trend in this age-group was a decline in NSAH-related mortality.