Abstract 4368312: Demographics and Trends in Reported Amyloidosis Mortality in the United States, 1999-2023

Background: Amyloidosis represents a heterogeneous group of disorders characterized by extracellular deposition of misfolded protein fibrils, leading to progressive organ dysfunction and death. Despite its clinical significance, there is a paucity of large-scale epidemiologic data characterizing mortality trends associated with amyloidosis in the United States. Objective: To evaluate temporal trends and demographic patterns in amyloidosis-related mortality across the US population from 1999 to 2023. Methods: This population-based, retrospective cohort study utilized publicly available mortality data from the Centers for Disease Control and Prevention (CDC) Wide-ranging Online Data for Epidemiologic Research (WONDER) database spanning from 1999 to 2023. The study included decedents of all ages in whom amyloidosis was listed as either an underlying or contributing cause of death on death certificates. The primary outcome was the age-adjusted mortality rate for amyloidosis-related deaths per 100,000 population. AAMRs were stratified by sex, race and ethnicity, US census region, state, place of death, and age group. Results: From 1999 to 2023, a total of 52,659 amyloidosis-related deaths were recorded in the US. Most deaths occurred in medical facilities and homes. The overall AAMR nearly doubled from 4.95 (95% CI: 4.68–5.21) in 1999 to 10.30 (95% CI: 9.99–10.60) in 2022. After an initial period of relative stability from 1999–2012, AAMRs significantly increased from 2012–2018 [ Annual percent changes (APC): 5.24; 95% CI: 3.87–10.36] and again from 2018–2023 [APC: 11.13; 95% CI: -48.67–17.07]. Males consistently exhibited higher mortality rates than females (8.24 vs. 4.20), and among racial/ethnic groups, NH Black individuals had the highest AAMR (11.26), while NH Asians had the lowest (3.46). Since 2014, all U.S. census regions have shown a significant rise in amyloidosis-related AAMRs, following earlier periods of stability or modest increases. States such as Massachusetts, Vermont, Minnesota, and the District of Columbia exhibited the highest mortality burdens, whereas states like Louisiana, Arkansas, and Mississippi had the lowest. Mortality rates increased with advancing age, with individuals aged ≥85 years exhibiting the highest crude mortality rate (CMR: 64.29). Conclusion: Amyloidosis-related mortality has markedly increased over the past two decades in the US, with significant disparities across sex, age, racial/ethnic, and geographic groups.