Mortality Trends and Disparities in Cardiovascular Disease and Amyloidosis in the US (1999–2020)

Overview

This retrospective study analyzed 26,391 deaths in U.S. adults aged 25 and older where amyloidosis and cardiovascular disease (CVD) were co-coded from 1999 to 2020. The age-adjusted mortality rate (AAMR) nearly doubled over this period, with notable increases after 2012 and significant disparities by sex, race, geography, and urbanization.

Background

Amyloidosis, characterized by extracellular deposition of misfolded proteins such as transthyretin (ATTR) and immunoglobulin light chains (AL), is increasingly recognized as a contributor to cardiovascular morbidity, especially in older adults and those with heart failure with preserved ejection fraction (HFpEF). Advances in diagnostic imaging and novel therapies like TTR stabilizers and RNA-silencing agents have improved detection and management. Despite this, amyloidosis remains underdiagnosed and is associated with worse outcomes when coexisting with cardiovascular disease. Racial and socioeconomic disparities further complicate the burden of disease.

Data Highlights

Key Findings

• From 1999 to 2020, amyloidosis and CVD-related deaths increased from an AAMR of 4.4 to 9.31 per 1,000,000 adults aged ≥25 years.
• The overall average annual percent change (AAPC) in AAMR was 3.49% (95% CI: 3.15 to 3.78).
• A slight decrease in mortality occurred between 1999 and 2012 (APC: 0.54%, 95% CI: -0.37 to 1.17), followed by a moderate increase from 2012 to 2018 (APC: 6.81%, 95% CI: 0.59 to 8.23) and a significant rise until 2020 (APC: 13.60%).
• Black patients experience higher rates of hereditary ATTR amyloidosis due to the V122I mutation and face worse hospital outcomes, indicating racial disparities.
• Urbanization and geographic region influenced mortality rates, with variations observed across states and metropolitan versus rural areas.
• Deaths were recorded across multiple settings including hospitals, private residences, hospices, nursing homes, and long-term care facilities.

Clinical Implications

Clinicians should maintain a high index of suspicion for amyloidosis in patients with cardiovascular disease, particularly older adults and those with HFpEF, to enable timely diagnosis and initiation of disease-modifying therapies. Awareness of racial and geographic disparities is crucial to address inequities in access to advanced diagnostics and treatments. Enhanced screening and targeted interventions in high-risk populations may improve outcomes.

Conclusion

Amyloidosis coexisting with cardiovascular disease represents a growing mortality burden in the United States, with increasing trends over two decades and significant demographic disparities. Improved recognition and equitable access to emerging therapies are essential to mitigate this public health challenge.

References

1. Gertz et al. 2024 -- Advances in Amyloidosis Diagnosis and Treatment
2. CDC WONDER Database 1999-2020 -- Mortality Data
3. National Cancer Institute Joinpoint Regression Program -- Statistical Methods
4. Racial Disparities in ATTR Amyloidosis Outcomes -- Clinical Observations