Trends and Disparities in Amyloidosis and Cardiovascular Disease Mortality: A Population-Based Retrospective Study in the United States (1999–2020)

Introduction : Cardiac amyloidosis (CA), most commonly caused by transthyretin (ATTR) or light chain (AL) deposition, is increasingly recognized as a contributor to heart failure, particularly in older adults and patients with heart failure with preserved ejection fraction (HFpEF). Despite advances in diagnostic imaging and disease-modifying therapies, CA remains underdiagnosed, and population-level data on its combined mortality burden with cardiovascular disease (CVD) are limited. Aims : This study aimed to analyze two decades of consecutive mortality data to investigate amyloidosis and cardiovascular disease (CVD) across the United States (US), identifying patterns and disparities in mortality rates. Methods : A retrospective analysis was conducted using mortality data from the CDC WONDER database spanning 1999–2020. Age-adjusted mortality rates (AAMRs) per 1,000,000 persons were calculated, and trends were assessed using Average Annual Percentage Change (AAPC) and Annual Percent Change (APC) using Joinpoint 5.0.2. Results : Between 1999 and 2020, 26,391 Amyloidosis and CVD-related deaths occurred among adults aged 25 and older in the US. The overall AAMR for Amyloidosis and CVD-related mortality increased from 4.40 in 1999 to 9.31 in 2020, with an AAPC of 3.49 (p < 0.001). Most striking was the recent steep rise in AAMRs from 2018 to 2020 with an APC of 13.60. Men exhibited higher AAMRs compared to women. Similar to the overall trend, AAMRs for both men and women had a steep incline in the last decade. African Americans or Blacks had the highest AAMRs (11.4) followed by White (5.11) and Hispanics (3.86). The highest mortality was in the Northeast region (AAMR: 6.71). Nonmetropolitan areas had higher AAMRs than metropolitan areas (5.73 vs 4.76), however, with a more remarkable increase in metropolitan areas. Conclusions :The prevalence of amyloidosis and cardiovascular disease-related deaths has risen markedly, especially between 2018 and 2020. Increased mortality rates were noted among men, African Americans, and individuals in the Northeast region. These patterns emphasize the necessity for focused public health initiatives.