Cardiovascular Mortality in Amyloidosis: Long-Term Trends, Disparities, and Projections in the United States.

BackgroundCardiac involvement is a major determinant of prognosis in systemic amyloidosis, but population-level trends in cardiovascular mortality remain insufficiently characterized.MethodsWe performed a retrospective, population-based analysis of U.S. adults aged ≥45 years with amyloidosis using death certificate data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database from 1999 through 2023. Cardiovascular disease (CVD)-related deaths were identified using ICD-10 codes and classified into heart failure (HF), atrial fibrillation/flutter (AF), ischemic heart disease (IHD), or other CVD categories. Age-adjusted mortality rates (AAMRs) were calculated using the 2000 U.S. standard population. Joinpoint regression assessed temporal trends, and autoregressive integrated moving average (ARIMA) models projected mortality through 2033.ResultsA total of 35,222 CVD-related deaths occurred among adults with amyloidosis during the study period, yielding an overall AAMR of 1.12 per 100,000 population. Cardiovascular mortality increased nearly threefold, from 0.80 per 100,000 in 1999 to 2.27 per 100,000 in 2023, with a marked acceleration beginning in the late 2010s. HF consistently accounted for the largest proportion of CVD-related deaths. Mortality rates were higher among males, older adults, and non-Hispanic Black individuals, with demographic and geographic disparities widening over time. Similar upward trajectories were observed across U.S. Census regions and levels of urbanization. Projections indicated continued increases in cardiovascular mortality through 2033.ConclusionCardiovascular mortality among U.S. adults with amyloidosis has increased substantially over the past 25 years, with recent acceleration and persistent population-level disparities. These findings highlight a growing public health burden and support earlier detection, equitable access to specialized care, and continued national surveillance.