# Cardiovascular disease after Hodgkin lymphoma treatment: 40-year disease risk

Source: https://onco.cc/key-papers/paper-van-nimwegen-cardiovascular-disease-after-hodgkin-jama-intern-med-2015/  
OnCo record `paper-van-nimwegen-cardiovascular-disease-after-hodgkin-jama-intern-med-2015` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Half of 2,524 people treated for Hodgkin lymphoma developed heart or valve disease within forty years, and the risk was still four to six times the general population's after thirty-five years.

## Summary

The companion to the second-cancer cohort, from the same Dutch group. 2,524 patients diagnosed with Hodgkin lymphoma before the age of 51 (median 27.3 years) between 1965 and 1995, who survived at least five years, were followed through medical records and general practitioners, with cardiovascular events graded by the Common Terminology Criteria for Adverse Events version 4.0.

After a median follow-up of 20 years, 1,713 cardiovascular events occurred in 797 patients. At 35 years or more, the standardised incidence ratio for coronary heart disease or heart failure was still four to six times the general population rate, corresponding to 857 excess events per 10,000 person-years. The 40-year cumulative incidence of cardiovascular disease within the cohort was 50 per cent (95 per cent confidence interval 47 to 52), and 51 per cent of those affected had more than one event. For patients treated before the age of 25, cumulative incidences at 60 years or older were 20 per cent for coronary heart disease, 31 per cent for valvular heart disease and 11 per cent for heart failure as first events.

Mediastinal radiotherapy raised the risk of coronary heart disease (hazard ratio 2.7, 2.0 to 3.7), valvular heart disease (6.6, 4.0 to 10.8) and heart failure (2.7, 1.6 to 4.8). Anthracycline-containing chemotherapy raised valvular heart disease (1.5, 1.1 to 2.1) and heart failure (3.0, 1.9 to 4.7). The joint effects of mediastinal radiotherapy, anthracyclines and smoking appeared additive, which is the finding a survivor can act on.

## Fields

- Kind: Key paper
- Last checked: 2026-10-01
- Also known as: van Nimwegen 2015; Dutch Hodgkin cardiovascular cohort
- Tags: lymphoma-evidence
- Journal: JAMA Internal Medicine
- Year: 2015
- DOI: 10.1001/jamainternmed.2015.1180
- Authors: van Nimwegen FA, Schaapveld M, Janus CP, et al.
- Findings: 1,713 cardiovascular events occurred in 797 of 2,524 Hodgkin lymphoma survivors after a median follow-up of 20 years.; At 35 years or more after treatment, the standardised incidence ratio for coronary heart disease or heart failure remained four to six times the general population rate, or 857 excess events per 10,000 person-years.; The 40-year cumulative incidence of cardiovascular disease within the cohort was 50 per cent (95 per cent confidence interval 47 to 52), and 51 per cent of affected patients had multiple events.; Mediastinal radiotherapy raised the hazard of coronary heart disease to 2.7, valvular heart disease to 6.6 and heart failure to 2.7.; Anthracycline-containing chemotherapy raised the hazard of valvular heart disease to 1.5 and heart failure to 3.0.; The joint effects of mediastinal radiotherapy, anthracyclines and smoking appeared additive.
- What it means: The reason cardiac surveillance belongs in Hodgkin lymphoma survivorship care, the reason smoking cessation is a specific intervention for this group rather than general advice, and part of the reason modern protocols try to limit both mediastinal radiation and cumulative anthracycline dose.
- Caveats: Patients treated between 1965 and 1995 with radiotherapy fields far larger than those used today; absolute risks for people treated now should be lower, though by how much is unknown.; Observational, with the confounding by smoking and other cardiovascular risk factors that implies, although smoking was examined explicitly.; Event ascertainment relied on medical records and general practitioners, so milder events may be undercounted.

## Sources

- JAMA Internal Medicine 2015: https://doi.org/10.1001/jamainternmed.2015.1180
- PubMed: https://pubmed.ncbi.nlm.nih.gov/25915855/
- Europe PMC: https://europepmc.org/article/MED/25915855

## Connected records

- key papers: [Breast cancer following radiotherapy and chemotherapy among young women with Hodgkin disease](https://onco.cc/key-papers/paper-travis-breast-cancer-after-hodgkin-radiotherapy-jama-2003/), [Second cancer risk up to 40 years after treatment for Hodgkin's lymphoma](https://onco.cc/key-papers/paper-schaapveld-second-cancer-risk-40-years-hodgkin-nejm-2015/)
- roadmaps: [Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting](https://onco.cc/roadmaps/lymphoma-roadmap/)
- cancers: [Advanced-stage classical Hodgkin lymphoma (stage III to IV)](https://onco.cc/cancers/advanced-stage-classical-hodgkin-lymphoma/), [Early-stage classical Hodgkin lymphoma (stage I to II)](https://onco.cc/cancers/early-stage-classical-hodgkin-lymphoma/), [Hodgkin lymphoma](https://onco.cc/cancers/hodgkin-lymphoma/)
- fronts: [Radiation Therapy](https://onco.cc/fronts/radiation/), [Supportive Care & Survivorship](https://onco.cc/fronts/supportive-care/)
- terms: [Radiotherapy](https://onco.cc/terms/radiotherapy/)
- technologies: [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Proton therapy](https://onco.cc/technologies/proton-therapy/)
- drugs: [Doxorubicin](https://onco.cc/drugs/doxorubicin/)
- trials: [GHSG HD10](https://onco.cc/trials/hd10/), [GHSG HD16](https://onco.cc/trials/hd16/), [RADAR](https://onco.cc/trials/radar-hodgkin/)
- bottlenecks: [Older and multimorbid patients are excluded and undertreated](https://onco.cc/bottlenecks/b-aging-comorbidity/), [Survivorship and late effects are neglected](https://onco.cc/bottlenecks/b-survivorship/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- journals: [JAMA Internal Medicine](https://onco.cc/journals/jama-internal-medicine/)
- ideas: [Measure the late effects of the treatments being given now, not the ones given in 1975](https://onco.cc/ideas/lymphoma-ev-late-effects-of-the-treatments-given-now/)

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