What is the clinical evidence from this study?

Study design: Observational. Population: Multiple myeloma and cardiovascular disease (n=117907). Primary outcome: Average annual percent change (AAPC) in age-adjusted cardiovascular mortality rate (AAPC +0.04%, 95% CI -0.22 to 0.31).

What does this research mean for the field?

Overall cardiovascular mortality among adults with multiple myeloma remained stable from 1999 to 2023, despite significant increases in specific subtypes such as hypertensive, arrhythmic, and heart failure mortality. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

December 5, 2025Open Access

Temporal trends and disparities in cardiovascular disease-related mortality among adults with multiple myeloma in the United States, 1999–2023

Key Result

Overall cardiovascular mortality among adults with multiple myeloma remained stable from 1999 to 2023 (AAPC +0.04%), despite significant increases in hypertensive, arrhythmic, and heart failure mortality.

Study Design

Type

Observational (n=117,907)

Structured PICO

Population

U.S. adults aged ≥ 45 years with multiple myeloma (MM) and cardiovascular disease (CVD) as underlying or contributing causes of death (n=117,907 deaths)

Outcome

Cardiovascular disease-related mortality (Age-adjusted mortality rates per 100,000 population)hard clinical

While overall CVD mortality in multiple myeloma patients remained stable over 25 years, significant racial disparities persist and recent increases in specific cardiovascular mortalities highlight the need for integrated cardio-oncology care.

Main Result

Effect estimate: AAPC +0.04% (95% CI -0.22 to 0.31)

Limitations

Ecological nature of death certificate data lacking individual-level treatment exposures and COVID-19 infection status
Inability to establish causal relationships between treatments and mortality trends
Potential that observed increases in certain CVD mortality subtypes may partly reflect improved detection and documentation practices rather than solely true incidence increases

Abstract

BACKGROUND: Novel therapeutic agents have substantially improved multiple myeloma (MM) survival, making cardiovascular disease (CVD) a predominant cause of non-cancer mortality. Because MM predominantly affects older adults (median age 69 years) at elevated cardiovascular risk, we focused on adults aged ≥ 45 years. Comprehensive national data on temporal trends and demographic disparities in CVD-related mortality among MM patients remain limited. METHODS: We conducted a retrospective analysis using CDC WONDER Multiple Cause-of-Death database data (1999-2023) for U.S. adults aged ≥ 45 years with MM and CVD as underlying or contributing causes of death. Age-adjusted mortality rates (AAMRs) per 100,000 population were standardized to the 2000 U.S. standard population using the direct method. Joinpoint regression analysis identified temporal changepoints and calculated annual percent changes (APCs) and average annual percent changes (AAPCs). RESULTS: Among 117,907 CVD-related deaths in MM patients, overall AAMR was 3.92 per 100,000 (95% CI: 3.80-4.03) with no significant long-term change (AAPC + 0.04%). Joinpoint analysis revealed five phases: non-significant increase from 1999 to 2001 (APC + 3.10%), significant decline from 2001 to 2009 (APC - 2.05%), stability from 2009 to 2018 (APC + 0.16%), marked increase from 2018 to 2021 (APC + 6.70%, P < 0.05), and significant decline from 2021 to 2023 (APC - 4.59%). Males had significantly higher mortality than females (5.23 vs. 2.98 per 100,000; P < 0.001). Non-Hispanic Black adults experienced highest burden (8.38 per 100,000), 2.4-fold higher than non-Hispanic White adults (3.51 per 100,000). Mortality increased significantly with age (P < 0.001 for trend), reaching 18.46 per 100,000 in adults ≥ 85 years. Hypertensive diseases (AAPC + 4.79%) and cardiac arrhythmias (AAPC + 3.71%) showed largest increases, while ischemic heart diseases (AAPC - 1.15%) and cerebrovascular diseases (AAPC - 1.07%) declined. Geographic analysis revealed the highest mortality rates in the Northeast (4.29 per 100,000) and West (4.14 per 100,000). CONCLUSIONS: Although overall CVD mortality remained stable over 25 years, concerning increases in hypertensive, arrhythmic, thromboembolic, and heart failure mortality during 2018-2021 coincided with expanded cardiotoxic therapy use and COVID-19 disruptions. These findings highlight the importance of incorporating baseline cardiovascular risk assessment and longitudinal surveillance into MM treatment pathways, ensuring adherence to guideline-based thromboprophylaxis, and developing multidisciplinary cardio-oncology models that address persistent racial and ethnic disparities in cardiovascular outcomes.

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