Demographics and Trends in Reported Amyloidosis-related Mortality in the United States, 1999-2023

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. We sought to evaluate temporal trends and demographic patterns in amyloidosis-related mortality across the US population from 1999 to 2023.

This population-based, retrospective cohort study used publicly available mortality data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research database spanning from 1999 to 2023. The study included individuals 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. Age-adjusted mortality rates (AAMRs) were stratified by sex, race and ethnicity, US census region, state, place of death, and age group. Annual percentage changes (APCs) and 95% confidence intervals (CIs) were calculated to assess temporal trends.

From 1999 to 2023, a total of 52,659 amyloidosis-related deaths were recorded in the United States. 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 to 2012, AAMRs significantly increased from 2012 to 2018 (APC 5.24; 95% CI 3.87-10.36) and again from 2018 to 2023 (APC 11.13; 95% CI -48.67 to 17.07). Male patients consistently exhibited greater mortality rates than female patients (8.24 vs 4.20), and among racial/ethnic groups, non-Hispanic Black individuals had the greatest AAMR (11.26), whereas non-Hispanic Asians had the lowest (3.46). Since 2014, all US census regions have shown a significant increase in amyloidosis-related AAMRs, after earlier periods of stability or modest increases. States such as Massachusetts, Vermont, Minnesota, and the District of Columbia exhibited the greatest 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 greatest crude mortality rate (64.29).

Amyloidosis-related mortality has markedly increased over the past 2 decades in the United States, with significant disparities across sex, age, racial/ethnic, and geographic groups. These increasing mortality rates likely reflect heightened diagnostic recognition rather than therapeutic failure, underscoring the need for earlier diagnosis, equitable access to care, and targeted screening of high-risk populations.