Background

Myelodysplastic syndromes (MDS) are clonal hematopoietic neoplasms associated with substantial morbidity and mortality, particularly among older adults. Although leukemic transformation remains a major disease-related outcome, nonleukemic causes of death are increasingly recognized. Cardiovascular disease (CVD) can contribute substantially to mortality in patients with MDS due to advanced age, chronic inflammation, anemia-related physiologic stress, transfusion burden, iron overload, comorbidities, and treatment-related effects. Contemporary population-level estimates of excess cardiovascular mortality in MDS remain limited.

Methods

We conducted a retrospective population-based analysis of patients diagnosed with MDS using the Surveillance, Epidemiology, and End Results (SEER) database from 2000–2021. Cardiovascular mortality was defined using SEER cause-of-death categories, including diseases of the heart, hypertension-related cardiac disease, cerebrovascular disease, atherosclerosis, aortic aneurysm and dissection, and other arterial diseases. Expected cardiovascular deaths were derived from age-, sex-, and race-stratified cardiovascular mortality rates in the general US population. Standardized mortality ratios (SMRs) with 95% confidence intervals (CIs) were calculated overall and across demographic subgroups.

Results

A total of 84806 patients with MDS were included. During the study period, 64827 deaths occurred, representing 76.4% of the cohort. Cardiovascular disease accounted for 12165 deaths, comprising approximately 19% of all observed deaths. Overall, patients with MDS experienced markedly elevated cardiovascular mortality compared with the general US population, with an SMR of 25.3 (95% CI, 24.9–25.8), indicating an approximately 25-fold higher cardiovascular mortality than expected. Excess cardiovascular mortality was observed across demographic subgroups, including male patients (SMR, 27.7; 95% CI, 27.1–28.4) and female patients (SMR, 23.3; 95% CI, 22.7–24.0). Patients younger than 45 years had an SMR of 5.8 (95% CI, 4.5–7.5), while those aged 45 years or older had an SMR of 22.4 (95% CI, 22.0–22.8). By race and ethnicity, elevated SMRs were observed among White, Hispanic, Asian/Pacific Islander, Black, and American Indian/Alaska Native patients.

Conclusion

In this large SEER-based cohort of 84806 patients with MDS, cardiovascular disease represented a major nonleukemic cause of death, accounting for nearly one-fifth of all mortality. These findings highlight the need for proactive cardiovascular risk assessment and cardio-oncology collaboration in MDS care.