Cardiovascular Care for the Survivor of Hodgkin Lymphoma | Journal Scan

Study Questions:

Compared with cardiovascular disease incidence in the general population, what are the relative and absolute excess cardiovascular risks up to 40 years after treatment of Hodgkin Lymphoma (HL)?


This was a retrospective cohort study of 2,524 Dutch patients who were diagnosed as having HL at younger than 51 years of age. Eligible patients were those who were treated from 1965 to 1995 (prescribed treatment included mediastinal radiotherapy dose and anthracycline dose). Cardiovascular outcomes were identified from medical records for both the survivors and controls. Cardiovascular outcomes included the following: coronary heart disease (CHD), including myocardial infarction and angina pectoris; valvular heart disease (VHD); and heart failure (HF). The incidence of CHD and HF in the cohort was compared with age-, sex-, and calendar period-specific cardiovascular disease incidence rates for the Dutch population; reference incidence data were not available for VHD.


Median follow-up was 20 years; 1,713 cardiovascular events were identified in 797 patients. Compared to population controls, those who were treated for HL were at a significantly higher risk of developing CHD (standardized incidence ration [SIR], 3.2; 95% confidence interval [CI], 3.0-3.5) and HF (SIR, 6.8; 95% CI, 5.9-7.6). Highest relative risks were seen in patients treated before 25 years of age. In analyses adjusted for year of HL diagnosis, sex, and ever smoking, mediastinal radiotherapy and anthracycline-containing chemotherapy were associated with increased risk of any cardiovascular disease (hazard ratio [HR] for mediastinal radiotherapy, 3.6; 95% CI, 2.8-4.6; HR for anthracycline chemotherapy, 1.5; 95% CI, 1.2-1.8). The risk between mediastinal radiotherapy and cardiovascular disease risk (first event) was strongest for VHD (HR, 6.6; 95% CI, 4.0-10.8). Anthracycline-containing chemotherapy was associated with increased risks for VHD (HR, 1.5; 95% CI, 1.1-2.1) and HF (HR, 3.0; 95% CI, 1.9-4.7); it was not associated with CHD. There was no evidence of multiplicative interaction between mediastinal radiotherapy and anthracycline-containing chemotherapy for any cardiovascular disease. The combined effect of mediastinal radiotherapy, anthracyclines, and smoking was additive.


The authors concluded that survivors of HL are at increased risk of CHD, HF, and VHD at least 40 years after diagnosis.


This is an important study that reports cardiovascular disease incidence in survivors of HL over a significantly long duration (median follow-up of 20 years). The risk of developing CHD and HF, when compared to population controls, was significant. Certainly, this information should be used to inform follow-up of these patients. The synergistic effect of mediastinal radiotherapy, anthracyclines, and smoking should be a catalyst for even stronger efforts to promote smoking cessation in this group. Lastly, and as the authors of an accompanying commentary (Tonorezos E, Overholser L. Caring for the Adult Survivor of Hodgkin Lymphoma. JAMA Intern Med 2015;Apr 27:[Epub]) suggest, “We will need large, long-term prospective studies and randomized clinical trials to guide evidence-based practice in regard to defining the best approaches” for cardiovascular risk factor reduction in survivors of HL.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Valvular Heart Disease, Acute Heart Failure, Smoking

Keywords: Angina Pectoris, Anthracyclines, Cardiovascular Diseases, Cohort Studies, Coronary Disease, Follow-Up Studies, Heart Failure, Heart Valve Diseases, Hodgkin Disease, Incidence, Medical Records, Myocardial Infarction, Primary Prevention, Retrospective Studies, Risk, Risk Factors, Smoking, Smoking Cessation, Survivors

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