Racial, geographic, and gender disparities in ischemic heart disease mortality in patients with multiple myeloma: A nationwide analysis (1999–2023).

Abstract Background: Ischemic heart disease (IHD) is a leading causes of mortality in the United States. Patients with MM face elevated IHD risk due to treatment-induced cardiotoxicity, chronic inflammation, and overlapping cardiovascular risk factors. This study analyzes national trends in IHD-related mortality among MM patients from 1999 to 2023, focusing on disparities by sex, race/ethnicity, age, and geographic region. Methods: Data were obtained from the CDC WONDER Multiple Cause of Death database for U.S. adults aged ≥25 years from 1999 to 2023. Decedents with MM (ICD-10 code C90.0) and IHD (ICD-10 codes I20–I25) listed on the death certificate were included. Age-adjusted mortality rates (AAMRs) per million population were calculated. Joinpoint regression was used to estimate annual percent change (APC) and average annual percent change (AAPC) with 95% confidence intervals (CIs). Analyses were stratified by sex, race/ethnicity, age group, region, urbanization level, and state. Statistical significance was defined as p < 0.05. Results: A total of 30,107 deaths involving both MM and IHD were identified. The overall AAMR was 5.72 per million (95% CI: 5.32–5.58), ranging from a high of 6.80 in 2002 to a low of 4.49 in 2018. There was a significant overall decline (AAPC: –1.31; 95% CI: –2.99 to –0.39), although a non-significant increase was observed from 2018 to 2023 (APC: 6.62; 95% CI: –5.66 to 20.51; p = 0.28). Sex-specific analysis showed higher mortality in males (19,705 deaths) compared to females (10,402 deaths). Male AAMRs declined from 9.68 in 1999 to 8.28 in 2023, with a significant decrease from 1999 to 2018 (APC: –1.64; 95% CI: –2.02 to –1.25), followed by a non-significant rise (2018–2021: APC: 6.35) and a drop (2021–2023: APC: –4.13). Female AAMRs declined from 4.21 to 2.45, with a significant decrease from 1999 to 2015 (APC: –3.49; 95% CI: –4.27 to –2.71), followed by stable trends (2015–2023: APC: –0.0047; p = 0.997). Among racial/ethnic groups, Black or African American individuals had the highest AAMR (9.10; 95% CI: 7.73–10.47), with a significant decline (APC: –1.43; 95% CI: –2.02 to –0.84; p = 0.000048). White individuals had an AAMR of 5.27 (95% CI: 4.94–5.60), with a significant decline from 1999–2018 (APC: –2.01), followed by a non-significant rise (2018–2021: APC: 6.75) and subsequent drop (2021–2023: APC: –5.39). Hispanic or Latino individuals had the lowest AAMR (4.09; 95% CI: 3.09–5.31), with a significant decline from 1999 to 2023 (APC: –0.95; 95% CI: –1.70 to –0.20; p = 0.015). Age-specific analysis revealed the highest mortality in the ≥85-year age group, with declining trends observed in the 75–84 group. Regional analysis showed the Northeast consistently had the highest AAMRs, followed by the Midwest, West, and South. Conclusions: From 1999 to 2023, IHD-related mortality in MM patients declined overall, yet persistent disparities remain. Male, Black, and elderly patients continue to experience excess mortality related to IHD. These findings underscore the need for tailored cardiovascular risk mitigation and equitable access to care in high-risk MM populations.