What is the clinical evidence from this study?

Study design: Cohort. Population: Non-Hodgkin lymphoma (n=18189). Intervention: Non-Hodgkin lymphoma survivorship vs. Matched controls without cancer or cardiovascular disease. Primary outcome: Cardiomyopathy (HR 6.77, 95% CI 3.44-13.33).

What does this research mean for the field?

Adolescent and young adult survivors of non-Hodgkin lymphoma have a significantly higher risk of developing cardiovascular diseases, particularly cardiomyopathy and heart failure, compared to the general population. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

May 16, 2025Open Access

Cardiovascular disease in adolescent and young adult survivors of non-Hodgkin lymphoma in Korea

Key Result

Adolescent and young adult survivors of non-Hodgkin lymphoma had a significantly higher risk of cardiomyopathy (HR 6.77) and heart failure (HR 4.90) compared to matched controls.

Study Design

Type

Cohort (n=18,189)

Structured PICO

Does a history of non-Hodgkin lymphoma increase the risk of major adverse cardiovascular events in adolescent and young adult survivors compared to the general population?

Population

4,553 adolescent and young adult (aged 15-39 years) survivors of non-Hodgkin lymphoma diagnosed between 2006 and 2019, and 13,659 matched controls, mean age 29.5, 59% male, in Korea.

Intervention

History of non-Hodgkin lymphoma and its treatments (including hematopoietic stem cell transplantation, chemotherapy, radiotherapy)

Comparator

1:3 matched controls without a history of cancer or cardiovascular disease, matched based on age, sex, and residential area

Outcome

Major adverse cardiovascular events including myocardial infarction, cardiomyopathy, heart failure, ischemic stroke, and hemorrhagic strokehard clinical

Adolescent and young adult survivors of non-Hodgkin lymphoma face a substantially elevated long-term risk of cardiomyopathy, heart failure, and hemorrhagic stroke, underscoring the need for cardiovascular surveillance.

Main Result

Effect estimate: HR 6.77 (95% CI 3.44-13.33)

Absolute Event Rate: 0.1% vs 0%

Limitations

Use of claims data limited access to certain clinical details, including disease stage at diagnosis and information on relapses
Detailed treatment-related data, such as chemotherapy regimens and dosages, radiation type and intensity, and conditioning regimens for HSCT, were unavailable
Potential misclassification of exposures and outcomes based on operational criteria
No formal adjustments for multiple comparisons were applied
Unmeasured confounders, such as genetic factors, family history, and behavioral factors, may have influenced the results

Abstract

PURPOSE: Long-term cardiovascular risk in adolescent and young adult (AYA) survivors of non-Hodgkin lymphoma (NHL) remains insufficiently characterized. This retrospective cohort study investigated the incidence of cardiovascular disease (CVD) among AYA survivors of NHL. METHODS: We identified 4553 individuals aged 15-39 years diagnosed with NHL between 2006 and 2019 using the Korean National Health Insurance System database. A control group of 13,659 individuals without a history of cancer or CVD was selected using 1:3 matching based on age, sex, and residential area. The primary outcomes were major adverse cardiovascular events such as myocardial infarction, cardiomyopathy, heart failure, ischemic stroke, and hemorrhagic stroke. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. RESULTS: The mean (SD) age of the participants was 29.5 (6.8) years, and 59% were male. Over a median follow-up of 6.5 years, survivors of NHL had significantly higher risks of cardiomyopathy (HR 6.77; 95% CI 3.44-13.33), heart failure (HR 4.90; 95% CI 3.45-6.97), and hemorrhagic stroke (HR 3.14; 95% CI 1.75-5.65), compared to controls. In the subgroup analyses stratified by treatment modality, the highest risks were observed among patients who underwent hematopoietic stem cell transplantation, which involved high-dose chemotherapy with or without radiotherapy. The risk of myocardial infarction and ischemic stroke did not increase significantly. CONCLUSION: AYA survivors of NHL had a significantly higher risk of CVD, including cardiomyopathy, heart failure, and hemorrhagic stroke, than the general population. IMPLICATIONS FOR CANCER SURVIVORS: Long-term cardiovascular surveillance is essential for AYA survivors of NHL, particularly those receiving intensive treatment.

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