Cardiovascular disease after Hodgkin lymphoma treatment: 40-year disease risk.
OBJECTIVE
Hodgkin lymphoma (HL) survivors are at increased risk of cardiovascular diseases. It is unclear, however, how long the increased risk persists and what the risk factors are for various cardiovascular diseases.


OBJECTIVE
To examine relative and absolute excess risk up to 40 years since HL treatment compared with cardiovascular disease incidence in the general population and to study treatment-related risk factors for different cardiovascular diseases.


METHODS
This retrospective cohort study included 2524 Dutch patients diagnosed as having HL at younger than 51 years (median age, 27.3 years) who had been treated from January 1, 1965, through December 31, 1995, and had survived for 5 years since their diagnosis.


METHODS
Treatment for HL, including prescribed mediastinal radiotherapy dose and anthracycline dose.


METHODS
Data were collected from medical records and general practitioners. Cardiovascular events, including coronary heart disease (CHD), valvular heart disease (VHD), and cardiomyopathy and congestive heart failure (HF), were graded according to the Common Terminology Criteria for Adverse Events, version 4.0.


RESULTS
After a median follow-up of 20 years, we identified 1713 cardiovascular events in 797 patients. After 35 years or more, patients still had a 4- to 6-fold increased standardized incidence ratio of CHD or HF compared with the general population, corresponding to 857 excess events per 10,000 person-years. Highest relative risks were seen in patients treated before 25 years of age, but substantial absolute excess risks were also observed for patients treated at older ages. Within the cohort, the 40-year cumulative incidence of cardiovascular diseases was 50% (95% CI, 47%-52%). Fifty-one percent of patients with a cardiovascular disease developed multiple events. For patients treated before 25 years of age, cumulative incidences at 60 years or older were 20%, 31%, and 11% for CHD, VHD, and HF as first events, respectively. Mediastinal radiotherapy increased the risks of CHD (hazard ratio [HR], 2.7; 95% CI, 2.0-3.7), VHD (HR, 6.6; 95% CI, 4.0-10.8), and HF (HR, 2.7; 95% CI, 1.6-4.8), and anthracycline-containing chemotherapy increased the risks of VHD (HR, 1.5; 95% CI, 1.1-2.1) and HF (HR, 3.0; 95% CI, 1.9-4.7) as first events compared with patients not treated with mediastinal radiotherapy or anthracyclines, respectively. Joint effects of mediastinal radiotherapy, anthracyclines, and smoking appeared to be additive.


CONCLUSIONS
Throughout their lives, HL survivors treated at adolescence or adulthood are at high risk for various cardiovascular diseases. Physicians and patients should be aware of this persistently increased risk.
Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam.
Frederika A
FA
van Nimwegen
Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam2Comprehensive Cancer Centre, the Netherlands, Amsterdam.
Michael
M
Schaapveld
Department of Radiation Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
Cécile P M
CP
Janus
Department of Clinical Oncology, Leiden University Medical Center, Leiden, the Netherlands.
Augustinus D G
AD
Krol
Department of Hematology, University Medical Center Utrecht, Utrecht, the Netherlands.
Eefke J
EJ
Petersen
Department of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands.
John M M
JM
Raemaekers
Department of Cardiology, Amsterdam Medical Center, Amsterdam, the Netherlands.
Wouter E M
WE
Kok
Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam.
Berthe M P
BM
Aleman
Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam.
Flora E
FE
van Leeuwen
D000293:Adolescent; D000328:Adult; D018943:Anthracyclines / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006689:Hodgkin Disease / Q000628:therapy*; D006801:Humans; D015994:Incidence; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D011878:Radiotherapy / Q000009:adverse effects*; D018570:Risk Assessment; D012307:Risk Factors; D055815:Young Adult
D018943:Anthracyclines; D000970:Antineoplastic Agents