Abstract 1283: Asymmetric emergence of cardiovascular disease in hematologic malignancy survivors: A national real-world analysis

Abstract Background: The link between hematologic malignancies and cardiovascular disease (CVD) is recognized as bidirectional, wherein each condition potentially promoting the onset of the other, thereby creating a complex interplay with significant clinical implications. However, the comparative risk and temporal dynamics of these situations are not clearly established in extensive, heterogeneous populations. Methods: We utilized Electronic Health Record (EHR) data from the All of Us Research Program to construct two real-world cohorts: 5,786 hematologic malignancy survivors (leukemia, lymphoma, multiple myeloma, myelodysplastic syndromes MDS) without a history of CVD, and 77,617 CVD patients free of prior blood cancer. We assessed the bidirectional risk of incident disease in both modalities by comparing cumulative incidence, median time-to-event, and risk ratios (RRs), while adjusting for disease subtype, age, sex, race, and socioeconomic status. Results: Among 5,786 hematologic malignancy survivors, 1,881 (32.5%) experienced new-onset CVD throughout 20-years. The risk was predominantly exhibited in the initial phase, with cumulative incidence reaching 14.7% by year 2, 22.2% by year 5, and 27.7% by year 10. Conversely, merely 1,451 (1.87%) of CVD patients reported a hematologic malignancy by the tenth year. The progression to CVD occurred more rapidly than that of developing cancer after CVD (median: 2.4 vs. 4.0 years; P0.0001), indicating pronounced temporal asymmetry. The extent and duration of CVD risk are affected by the type of malignancy. Survivors of lymphoma and leukemia exhibited a relative risk approximately 20 times greater for developing CVD compared to the risk of cancer development in CVD patients (year 1 RR =19.1 and 20.6, respectively). Multiple myeloma survivors faced even higher risk (year 1 RR = 28.6), remaining elevated at year 10 (RR = 17.1). Among all subtypes, MDS conferred the highest risk during follow-up, with survivors ∼40 times more likely to develop CVD in the first year (year 1 RR = 39.9, year 10 RR = 19.9). The incidence of CVD subtypes also varied among hematologic malignancy survivors. Arrhythmias were the most frequent event (10-year incidence: 13.8%), followed by heart failure (8.9%). Patients aged 18-39 had a diminished risk relative to other age groups (OR: 0.78, 95% CI: 0.66-0.91), while female patients similarly demonstrated a reduced risk (OR: 0.86, 95% CI: 0.77-0.96) after controlling for race and ZIP code poverty level. Conclusion: Survivors of hematologic malignancies face an elevated, immediate risk of CVD that far exceeds the risk of developing cancer following CVD. This asymmetry indicates influences beyond common risk factors and emphasizes the critical necessity for integrated cardio-oncology monitoring, especially within the initial five years post-diagnosis, to alleviate this rapid cardiovascular decline. Citation Format: Yizhe Song, Pan Ma, Han Liang. Asymmetric emergence of cardiovascular disease in hematologic malignancy survivors: A national real-world analysis abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1283.