MON-827 Hypertension and Hormones: Decoding Mortality Trends Across the U.S. (1999-2020)

Disclosure: S. Yasmin: None. R. Ali: None. M. Zulqarnain: None. R. Noor: None. S. Cheema: None. S. Sahu: None. A. Dixit: None. S. Abdul Rehman Shah: None. S. Iftikhar: None. Introduction: The last several decades have seen an unprecedented increase in the incidence of obesity, affecting 40% of women and 35% of men in the United States (US). Considering 60-70% of obese patients have associated hyperlipidemia, both disorders entail a substantial healthcare burden. We aimed to determine trends and disparities of mortality rates of hyperlipidemia and obesity in the US from 1999-2020. Methods: We analyzed mortality trends for obesity and hyperlipidemia among adults aged 25+ using CDC WONDER data. Mortality rates were stratified by sex, region, race/ethnicity, states, place of death, and urbanization. We calculated crude mortality rates (CMR), age-adjusted mortality rates (AAMR), annual percent change (APC), and average annual percent change (AAPC), with statistical significance at p<0.05. Results: Obesity and hyperlipidemia accounted for 54089 fatalities throughout the study period. There was a significant sharp rise in the AAMR from 0.27 in 1999 to 0.59 in 2003 (APC: 22.04), followed by a significant steady rise to 1.39 in 2014 (APC: 8.53). From 2014 to 2018, the AAMR plateaued with a modest increase to 1.60 (APC: 1.83). Ultimately a significantly escalating upsurge was observed from 1.60 in 2018 to 2.48 in 2020 (APC:25.71) (AAPC: 11.19, 95% CI: 10.56 to 12.43, p<0.000001). This trend was similar across genders. Males (1.43) had higher AAMR than females (0.84), with a more pronounced increase in mortality rates after 2018, and an APC of 25.25. Overall, the age group 65-74 years revealed the highest CMR (3.08), followed by 75-84 years (2.85). Surprisingly, from 2018-2020, the age group 75-84 showed the highest mortality rates, with an APC of 26.07. When stratified by census regions, the Midwest region had the highest AAMR (1.28), followed by West (1.3), South (1.01), and Northeast (0.89). After 2018, the rise was observed across all regions but was particularly pronounced in the Northeast (APC:30.92). When stratified by race, Non-Hispanic (NH) American Indian had the highest AAMR (1.49), followed by NH Black (1.36), NH White (1.16), Hispanics (0.80) and lastly NH Asian (0.32). NH Black showed the steepest increase after 2018 (APC:32.37). Rural areas had higher AAMR (1.33) than urban (1.08), with a more pronounced rise in mortality observed in urban (AAPC: 11.14). The state of North Dakota had the highest AAMR of 2.82. Majority of deaths occurred at Decedent’s home (46.87%) Conclusion: Mortality has risen significantly over the past two decades, with a sharp surge after 2018. The disproportionately higher mortality rates among males, NH Blacks, the Northeast region, and urban areas underscore the need for targeted public health interventions. Further research is necessary to explore contributing factors and reduce mortality in these high-risk groups. Presentation: Sunday, July 13, 2025

Acute Myeloid Leukemia and sepsis-related mortality in the United States (U.S.) older adults: Nationwide trends and disparities over 25 years (1999 – 2023)

e19039 Background: Cardiovascular diseases (CVDs) are significant and burdensome complications of Hodgkin lymphoma (HL), contributing to increased mortality and morbidity. This study analyzed mortality trends and disparities due to HL and CVD among adults aged 25 and older from 1999to 2020. Methods: Using ICD-10 Codes C81 (Hodgkin Disease) AND I00-199 (Diseases of the circulatory system, crude and age-adjusted mortality rates (AAMR) per million were extracted from CDC WONDER and analysed across variables such as gender, race/ethnicity, year, state, census region, urbanization and place of death. Joinpoint regression software was employed to calculate the annual percent change (APC) and average annual percent change (AAPC). Results: A total of 12807 deaths were reported throughout the study period. The overall AAMR decreased from 3.35 in 1999 to 2.81 in 2020 with an AAPC of -0.75 (95% CI, -1.47 to -0.40). A significant decrease occurred from 1999 to 2018 ( APC: -1.61; 95% CI: -2.73 to -1.19), followed by a non-significant increase from 2018 to 2020 (APC: 7.83; 95% CI, -0.92 to 11.93). The AAMR for males was higher than for females (3.52 vs. 2.13), with a slower rate of decline for males (AAPC: -0.63) compared to females (AAPC: -1.32). Non-Hispanic (NH) White had the highest AAMR (2.89) followed by Hispanic (2.69), NH Black (2.30), NH American Indian (1.60), and lastly NH Asian (1.10). Among the US regions, the Northeast census region had the highest AAMR (3.20), followed by the West (2.95), Midwest (2.65), and lastly the South census region (2.35). Rural areas showed higher AAMR (2.83) than the urban areas (2.70). Rhode Island had the highest AAMR of 4.37. 56.27% of all fatalities occurred in medical facilities. Conclusions: Our analysis revealed notable discrepancies across age, sex, urbanization, race, and states in the United States, with an increase in mortality rate observed in the recent years. The stark differences in death rates by geography and demographics highlight a dire need for concentrated research and equitable distribution of resources. Deaths and age-adjusted mortality rates (AAMRs) per 1,000,000 for Hodgkin lymphoma and cardiovascular disease among adults in the United States between 1999 and 2020. Variable Variable Deatds (n) Total AAMR (95% CI) Deatds (n) Total AAMR (95% CI) Overall 12807 3.11 (3.08 to 3.14) Urbanization Sex Urban 10568 2.70 (2.65 to 2.75) Female 5486 2.35 (2.32 to 2.38) Rural 2239 2.83 (2.71 to 2.95) Male 7321 4.14 (4.09 to 4.19) Race/Ethnicity Census Region NH American Indians 44 1.60 (1.14 to 2.18) Northeast 2881 3.20 (3.08 to 3.32) NH Asians 207 1.10 (0.94 to 1.25) Midwest 2816 2.65 (2.55 to 2.75) NH Blacks 1122 2.30 (2.16 to 2.44) South 4053 2.35 (2.28 to 2.42) NH White 10347 2.89 (2.84 to 2.95) West 3057 2.95 (2.84 to 3.05) Hispanics 1053 2.69 (2.52 to 2.86)

e19567 Background: At diagnosis, around 20% of patients with multiple myeloma (MM) have impaired renal function. Renal failure (RF) is the leading cause of death in these patients, particularly among older adults. Despite the established correlation, mortality trends across various demographics in the United States is underexplored. This study examines mortality trends and discrepancies in MM and RF among older adults aged 55 and above from 1999 to 2020. Methods: Using the ICD-10 codes C90.0 (Multiple myeloma - Malignant neoplasms) and N17-N19 (Renal failure), we extracted crude mortality rate (CMR), and age adjusted mortality rate (AAMR) from CDC WONDER, stratified by gender, age, race, geographic areas, and urban/rural status from 1999 to 2020. Joinpoint regression was used to calculate annual percentage change (APC) and average annual percentage changes (AAPC). Results: A total of 49043 deaths were reported throughout the study period, with an overall AAMR of 3.11. A variable trend in mortality was observed, with an increasing trend from 1999 to 2003 (APC: 2.31) followed by a significantly decreasing trend from 2003 to 2020 (APC: -3.03;). The AAMR for males was double that of females (4.14 vs. 2.35), plus the rate of decline was less pronounced for males (AAPC: -1.80) than females (AAPC: -2.47). Non-Hispanic (NH) Blacks have the highest AAMR (6.89) and NH Asians the lowest (1.61). However, NH Whites showed the slowest rate of decline (AAPC -1.91). Geographically, the Midwest had the highest AAMR (3.24). Rural areas had slightly higher AAMRs than urban areas (3.17 vs. 3.06). The District of Columbia had the highest AAMR of 5.29. Most deaths occurred in medical facilities (55.51%). Lastly, the age group 85+ years old showed the highest CMR of 7.16 (AAPC= -0.74). Conclusions: Although there has been an overall decline in mortality related to MM and RF, the rate of decline has slowed in recent years. Higher AAMR was observed in males, the Midwest, the District of Columbia, rural areas, Black or African Americans, and geriatric age groups, indicating a need for targeted interventions in these groups to mitigate fatalities caused by MM and RF. Variable Variable Deaths (n) Total AAMR (95% CI) Deaths (n) Total AAMR (95% CI) Overall 49043 3.11 (3.08 to 3.14) Urbanization Sex Urban 40117 3.06 (3.03 to 3.09) Female 21313 2.35 (2.32 to 2.38) Rural 8926 3.17 (3.11 to 3.24) Male 27730 4.14 (4.09 to 4.19) Race/Ethnicity Census Region NH American Indians 256 3.12 (2.72 to 3.52) Northeast 9267 2.99 (2.93 to 3.05) NH Asians 960 1.61 (1.50 to 1.71) Midwest 11408 3.24 (3.18 to 3.30) NH Blacks 9746 6.89 (6.75 to 7.03) South 17961 3.07 (3.03 to 3.12) NH White 35092 2.77 (2.74 to 2.80) West 10407 3.07 (3.01 to 3.13) Hispanics 2906 2.57 (2.48 to 2.67)

Background: Diabetes mellitus (DM) is a major public health concern in the United States, with peripheral circulatory complications significantly contributing to morbidity and mortality. This study examines the temporal patterns and demographic disparities in mortality related to diabetes mellitus with peripheral circulatory complications in the U.S. from 1999 to 2020. Research question: What are the temporal trends and demographic disparities in mortality from diabetes mellitus with peripheral circulatory complications in the U.S. from 1999 to 2020? Methods: We performed a retrospective cohort study using death certificate data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research (CDC WONDER) database from 1999 to 2020. We calculated age-adjusted mortality rates (AAMRs), annual percent change (APC), and average annual percentage change (AAPC) per 1,000,000 persons. The data were stratified based on year, gender, ethnicity, and geographic area. Results: Between 1999 and 2020, peripheral circulatory complications in Diabetes Mellitus accounted for 99259 deaths among adults (≥25 years) in the United States. The overall AAMR for peripheral circulatory complications in Diabetes Mellitus-related deaths increased from 25.20 in 1999 to 25.4657 in 2004 (APC: 0.16; 95% CI: -2.61 to 7.03), after which it declined sharply to 14.91 in 2014 (APC: -5.12*; 95% CI: -8.18 to -4.03), and then increased again, sharply this time, to 25.28 in 2020 (APC: 7.51*; 95% CI: 5.18 to 10.60). Majority of the deaths occurred in medical facilities inpatient (33.8%). Men exhibited higher AAMRs compared to women (men: 27.5; women: 16.0). Highest Crude Mortality Rate (CMR) was seen in adults aged ≥ 85 years. Non-Hispanic (NH) American Indians showed the highest AAMRs (42.13), followed by NH Black (35.02), Hispanic (27.79), NH White (18.96), and NH Asian (10.41). Geographically, AAMRs ranged from 5.72 in Nevada to 34.97 in West Virginia, with Midwestern region having the highest mortality (AAMR: 24.43). Non-metropolitan areas exhibited higher AAMRs than Metropolitan areas (non-metropolitan: 25.86; Metropolitan: 19.73). Conclusion: After a period of decline (2004–2014), mortality from peripheral circulatory complications in adults with Diabetes Mellitus has risen since 2014, with notable disparities across racial and geographic groups. These trends highlight the need for targeted interventions and equitable healthcare access.

Background: Despite advances in HIV treatment, cardiac arrest remains a significant cause of mortality in people with HIV. However, national trends and disparities in cardiac arrest mortality associated with HIV in the United States (U.S.) remain understudied. Research Question: What are the trends and demographic disparities in cardiac arrest mortality associated with HIV among U.S. adults from 2004 to 2023? Aim: To examine trends and sociodemographic disparities in cardiac arrest mortality associated with HIV among U.S. adults from 2004 to 2023. Methods: We retrospectively analyzed the CDC WONDER database for adults aged ≥25 years between 2004 and 2023, where both cardiac arrest (ICD-10: I46) and HIV (ICD-10: B20–B24) were listed as causes of death. Age-adjusted mortality rates (AAMRs) were extracted per 100,000 persons. Annual percent change (APC) and average annual percent change (AAPC) were calculated using Joinpoint regression analysis, stratified by year, sex, race/ethnicity, and geographic region. Results: Between 2004 and 2023, 28,231 deaths were attributed to cardiac arrest associated with HIV among U.S. adults aged ≥25 years. The AAMR decreased from 1.2 in 2004 to 0.41 in 2023, with an AAPC of –5.48 (95% CI: –6.72 to –4.23; p < 0.0001). An initial steep decline was observed from 2004 to 2012 (APC: –9.93; p < 0.000001), followed by a modest decrease from 2012 to 2023 (APC: –2.12; p = 0.016). Men had a higher AAMR (0.96) than women (0.36), with a greater decline in women (AAPC: –6.34; p < 0.000001) compared to men (AAPC: –5.20; p < 0.000001). Racial disparities were evident, with Non-Hispanic (NH) Blacks having the highest AAMR (2.92), followed by Hispanics (0.84) and NH Whites (0.25). Regionally, the Northeast had the highest AAMR (1.2) and experienced the most significant decline (AAPC: –7.66; p < 0.000001), while the Midwest recorded the lowest AAMR (0.15). Metropolitan areas had slightly higher AAMRs (0.76) than nonmetropolitan areas (0.31). Most deaths occurred in medical facilities (67.8%), followed by at-home deaths (14.5%) and deaths in nursing homes or long-term care settings (11%). Conclusion: Cardiac arrest mortality associated with HIV has significantly declined from 2004 to 2023 across the U.S. However, disparities persist, with greater burdens observed among men, Non-Hispanic Black individuals, and residents of the South and metropolitan areas, emphasizing the need for targeted public health strategies.

Advances in cancer research and treatment access have led to decreasing cancer mortality in the US; however, cancer remains the leading cause of death among Hispanic individuals. To evaluate longitudinal cancer mortality trends from 1999 to 2020 among Hispanic individuals by demographic characteristics and to compare age-adjusted cancer death rates between the Hispanic population and other racial and ethnic populations during 2000, 2010, and 2020. This cross-sectional study obtained age-adjusted cancer death rates among Hispanic individuals of all ages between January 1999 and December 2020, using the Centers for Disease Control and Prevention WONDER database. Cancer death rates in other racial and ethnic populations were extracted for 2000, 2010, and 2020. Data were analyzed from October 2021 to December 2022. Age, gender, race, ethnicity, cancer type, and US census region. Trends and average annual percent changes (AAPCs) in age-adjusted cancer-specific mortality (CSM) rates among Hispanic individuals were estimated by cancer type, age, gender, and region. From 1999 to 2020, 12 644 869 patients died of cancer in the US, of whom 690 677 (5.5%) were Hispanic; 58 783 (0.5%) were non-Hispanic American Indian or Alaska Native; 305 386 (2.4%), non-Hispanic Asian or Pacific Islander; 1 439 259 (11.4%), non-Hispanic Black or African American; and 10 124 361 (80.1%), non-Hispanic White. For 26 403 patients (0.2%), no ethnicity was stated. The overall CSM rate among Hispanic individuals decreased by 1.3% (95% CI, 1.2%-1.3%) annually. Overall CSM rate decreased more for Hispanic men (AAPC, -1.6%; 95% CI, -1.7% to -1.5%) compared with women (AAPC, -1.0%; 95% CI, -1.0% to -0.9%). While death rates among Hispanic individuals decreased for most cancer types, mortality rates for liver cancer (AAPC, 1.0%; 95% CI, 0.6%-1.4%) increased among Hispanic men, and rates of liver (AAPC, 1.0%; 95% CI, 0.8%-1.3%), pancreas (AAPC, 0.2%; 95% CI, 0.1%-0.4%), and uterine (AAPC, 1.6%; 95% CI, 1.0%-2.3%) cancers increased among Hispanic women. Overall CSM rates increased for Hispanic men aged 25 to 34 years (AAPC, 0.7%; 95% CI, 0.3%-1.1%). By US region, liver cancer mortality rates increased significantly in the West for both Hispanic men (AAPC, 1.6%; 95% CI, 0.9%-2.2%) and Hispanic women (AAPC, 1.5%; 95% CI, 1.1%-1.9%). There were differential findings in mortality rates when comparing Hispanic individuals with individuals belonging to other racial and ethnic populations. In this cross-sectional study, despite overall CSM decreasing over 2 decades among Hispanic individuals, disaggregation of data demonstrated that rates of liver cancer deaths among Hispanic men and women and pancreas and uterine cancer deaths among Hispanic women increased from 1999 to 2020. There were also disparities in CSM rates among age groups and US regions. The findings suggest that sustainable solutions need to be implemented to reverse these trends among Hispanic populations.

Trends in comorbid mortality from disseminated intravascular coagulation and sepsis in United States adults: A population-based analysis using CDC wonder database

National temporal trends and demographic disparities in primary immunodeficiency-related mortality in the United States, 1999–2024

Introduction and Objective: Diabetes (DM) is an independent risk factor for ischemic heart disease (IHD). We aim to investigate disparities in diabetes-related ischemic heart disease (DRIHD) mortality trends within specific epidemiological groups. Methods: We extracted data from the CDC WONDER database from 1999 to 2020.IHD was listed as the main cause of death (ICD codes: I20-I25), while DM as a contributory cause (ICD codes: E10 -E14). We calculated the Age-Adjusted Mortality rate (AAMR) per 100,000 people and annual percentage change using Joinpoint regression. Results: About 1,094,046 Individuals with DM died of IHD from 1999-2020. The overall AAMR was 14.8. Males, non-Hispanic Blacks, individuals aged 75-84 years, and people who lived in Rural areas had significantly higher AAMR. AAMRs among census regions were comparable. The AAMR of the entire cohort declined from 20.2 to 13.6 over the study period (Average Annual Percentage Change (AAPC): -2.06; 95% CI: -2.34% to -1.90). Higher AAPCs were also observed in females and people living in urban areas. Conclusion: Although DM-related IHD mortality has declined over the past 2 decades, disparities persist among Males, non-Hispanic blacks, rural dwellers, and individuals aged 75-84 years. These findings underscore the need for longitudinal studies to explore the drivers of disparities and targeted public health interventions. Disclosure E. Okorigba: None. P.A. Kwaah: None. S.A. Mensah: None. E.A. Agyemang: None. A.K. Carboo: None. G. Appah: None. H. Rashid: None.

Background Despite the progress made in managing HIV, the mortality trends among general population in the US remains understudied. Our aim is to analyse the trends in HIV-related mortality among US residents by demographic characteristics and association with social vulnerability index (SVI). Methods We abstracted national mortality data from the multiple cause of death files in the CDC WONDER database. The ICD-10 Codes (B20-B24) were used to identify HIV deaths among US population from 1999 to 2023. Trends in age-adjusted mortality rate (AAMR) were assessed using Joinpoint regression analysis. For 10-year increment age-groups, crude mortality rates were reported. Results were expressed as annual percentage changes (APC), average annual percentage changes (AAPC), and 95% confidence intervals (CI). SVI was obtained from CDC for each county. Results Between 1999 and 2023, a total of 271,932 HIV-infected patients died within the US (AAMR= 3.4 per 100,000; 95% CI: 3.3–3.5). Overall mortality trends decreased at an annual rate of −4.34% (95% CI: −5.25, −3.41) from 1999 through 2023 in the whole population. Specifically, the trends are higher among males age groups 45–54 years (overall rising in age 65 and above), African Americans, South Region and Large metropolitan areas. States in the top 90th percentile included District of Columbia, Florida, Maryland, Louisiana, New York, and Georgia. Union county followed by Miami-Dade are highly affected within Florida State which ranks second after District of Columbia. SVI was independently associated with HIV mortality with strong association throughout the United States counties. Conclusions HIV mortality among US population has decreased overall from 1999 to 2023, but with varying trends by race and ethnicity. This highlights the need for enhanced public health surveillance to better understand the scope of HIV mortality and identify high-risk demographic and regional subgroups for targeted interventions.

Introduction: Coronary artery disease (CAD) is the third leading cause of death in the US for adults aged >35 years. Almost half of the adult US population has obesity, which predisposes to atherosclerosis and may lead to poor prognosis in CAD. We aim to identify CAD-related mortality trends in patients with obesity in the US stratified by age, sex, race, and geographical location. Methods: The CDC-WONDER database was used to extract death certificate data for adults aged ≥25 years. Crude mortality rates (CMR) and age-adjusted mortality rates (AAMRs) per 100,000 persons were calculated, and temporal trends were delineated by calculating annual percent change (APC) and the average APC (AAPC) in the rates using JoinPoint regression analysis. Results: From 1999 to 2020, a total of 182,436 CAD-related deaths occurred in individuals with obesity. The AAMR increased consistently from 1999 to 2018 (APC: 4.48) and surged thereafter till 2020 (APC: 13.91). The AAMR for males (4.91) was almost double that of females (2.76). Non-Hispanic (NH) American Indians or Alaska Natives displayed the highest AAMR (5.37) while NH Asians or Pacific Islanders displayed the lowest (0.88). NH Blacks or African Americans displayed an AAMR of 5.06, followed by NH Whites (3.88) and Hispanics or Latinos (2.6). AAMRs also varied substantially by region (Midwest: 4.09; West: 4; Northeast: 3.67; South: 3.53). States with the highest AAMRs were Vermont and Oklahoma. Non-metropolitan regions exhibited a higher AAMR (4.42) than metropolitan regions (3.64). The adults aged 65-74 years exhibited the greatest CMR (8.99). Conclusion: We observed increasing trends in CAD-related deaths in adults with obesity throughout the study period. The highest mortality was exhibited by males and NH American Indians or Alaska Natives, residents of the Midwest and non-metropolitan areas, and individuals aged 65-74 years. Better healthcare practices and lifestyle modifications should be promoted in these high-risk populations to reduce the CAD-related mortality rates in adults with obesity.

Mapping the past, predicting the future: Hematologic malignancy mortality trends (1968–2023) and forecasts through 2050 in older u.S adults

Background: Kidney cancer remains a significant contributor to cancer-related morbidity and mortality. Current projections estimate that the annual incidence will reach approximately 475,000 new cases by 2030. Furthermore, cardiovascular disease (CVD) is emerging as a leading non-cancer cause of death among kidney cancer patients, who face a nearly threefold higher risk of CVD-related mortality.This study aims to evaluate the shifting mortality landscape by examining the impact of CVD on overall mortality in patients with kidney cancer. Methods: A retrospective analysis of CVD-related mortality in kidney cancer patients was conducted using the CDC WONDER database from1999 to 2020. Age-Adjusted Mortality Rates (AAMRs) per 100,000 and Annual Percent Change (APCs) with 95% CIs were determined. Joinpoint regression analysis was employed to examine trends across various demographic and regional groups. Results: A total of 106,320 CVD-related mortality occurred in kidney cancer patients from 1999 to 2020, with 35.11% deaths occurring at the Decedent’s home. With an AAPC (Average Annual Percent Change) of 0.44 (95% CI: 0.23 to 0.72] the overall AAMR increased from 1.38 in 1999 to 1.58 in 2020. There was an upward trend between 1999 and 2006 (APC:0.71 CI: 0.01 to 2.96) followed by a downward trend till 2016 (APC:-0.85 CI:-2.82 to -0.43) followed by a significant increase till 2020 (APC:3.29 CI:1.69 to 6.49). Males consistently had higher AAMRs than females (2.19 vs 0.88). AAMRs differed markedly by race, with the highest rate among NH-American Indian or Alaska Native (1.95), followed by NH-Black or African American (1.58), NH-White (1.43), Hispanic (1.38), and the lowest in NH-Asian or Pacific Islander (0.74). The greatest rise in mortality was observed in NH-Black or African American from 2018-2020 (APC:6.17 CI:-0.66 to 10.36). 35-44 year age group had an overall rise from 1999-2020 (APC:1.04 CI:-0.03 to 2.18). Nonmetropolitan areas had the greatest increase from 1999-2020 (AAPC:1.39). Rhode Island, North Dakota, California, Oklahoma, Mississippi, and Nebraska exhibited AAMRs nearly twice as high as those in states within the lowest 10th percentile. Conclusion: CVD-related mortality among kidney cancer patients presents with a concerning upward trend, with persistent demographic and geographic disparities. These trends further necessitate an integrated cardio-oncology approach to improve survival outcomes associated with two of the leading causes of death.

Introduction: Hepatocellular carcinoma (HCC), predominantly arising in the setting of cirrhosis, constitutes a formidable oncologic burden, with mortality patterns shaped by evolving epidemiological factors. Delineating mortality patterns and demographic differentials is imperative for addressing underlying inequities and informing precise public health strategies. Methods: The CDC WONDER database was queried for deaths attributed to HCC with concomitant cirrhosis in adults (≥25 years) from 1999 to 2020. Age-adjusted mortality rates (AAMRs), standardized per 1,000,000 individuals, were examined, and joinpoint regression analysis was employed to compute annual percent changes (APCs), with particular emphasis on disparities stratified by sex, race, and geographic region. Results: Between 1999 and 2020, HCC mortality among cirrhotic patients exhibited a substantial rise, with AAMR escalating from 6.9 to 15.2 per 1,000,000, corresponding to an average annual percent change (AAPC) of 3.64 (95% CI: 3.41-3.95, P < 0.000001). Gender disparities were pronounced, with men bearing a consistently elevated mortality burden throughout the study period (average AAMR men: 18.8 vs women: 4). Nonetheless, the overarching progression remained analogous between genders (AAPC men: 3.56 vs women: 3.94, P < 0.000001), characterized by a notably steep inflation following 2005. Racial heterogeneity was also evident, wherein non-Hispanic White individuals exhibited a uniquely upward trajectory throughout the study period (AAPC: 4.13, P < 0.000001), contrary to Asians who experienced a marginal, insignificant decline (AAPC -0.05, P = 0.96). Despite an initial regression, Hispanic individuals, overall, exhibited the highest mortality rate (AAMR: 22.3), abruptly ascending between 2007 and 2018 (APC: 4.37, P < 0.000001), while Black individuals also showed an overall increase (AAPC 3.20, P = 0.000001). Geographically, AAMRs spanned from 6 in Mississippi to 20.4 in Texas, and the Western Region exhibited the highest average AAMR at 14.3. Conclusion: These findings reveal a concerning rise in HCC-related mortality in patients with cirrhosis over the past 2 decades, driven by a disproportionate burden, underscoring the need for targeted surveillance and equitable care to mitigate the growing impact of HCC in the United States.