title: Long-term risk of cardiovascular disease in 5-year survivors of testicular cancer.
abstract: OBJECTIVE
  To evaluate the long-term risk of cardiovascular disease (CVD) in survivors of testicular cancer (TC).
  
  
  METHODS
  We compared CVD incidence in 2,512 5-year survivors of TC, who were treated between 1965 and 1995, with general population rates. Treatment effects on CVD risk were quantified in multivariate Cox regression analysis.
  
  
  RESULTS
  After a median follow-up of 18.4 years, 694 cardiovascular events occurred, including 141 acute myocardial infarctions (MIs). The standardized incidence ratio (SIR) for coronary heart disease was 1.17 (95% CI, 1.04 to 1.31), with 14 excess cases per 10,000 person-years. The SIR for MI was significantly increased in nonseminoma survivors with attained ages of less than 45 (SIR = 2.06) and 45 to 54 years (SIR = 1.86) but significantly decreased for survivors with attained ages of 55 years or older (SIR = 0.53). In Cox analysis, mediastinal irradiation was associated with a 3.7-fold (95% CI, 2.2- to 6.2-fold) increased MI risk compared with surgery alone, whereas infradiaphragmatic irradiation was not associated with an increased MI risk. Cisplatin, vinblastine, and bleomycin (PVB) chemotherapy (CT) was associated with a 1.9-fold (95% CI, 1.7- to 2.0-fold) increased MI risk, and bleomycin, etoposide, and cisplatin (BEP) CT was associated with a 1.5-fold (95% CI, 1.0- to 2.2-fold) increased CVD risk and was not associated with increased MI risk (hazard ratio = 1.2; 95% CI, 0.7 to 2.1). Recent smoking was associated with a 2.6-fold (95% CI, 1.8- to 3.9-fold) increased MI risk.
  
  
  CONCLUSIONS
  Nonseminomatous TC survivors experience a moderately increased MI risk at young ages. Physicians should be aware of excess CVD risk associated with mediastinal radiotherapy, PVB CT, and recent smoking. Intervention in modifiable cardiovascular risk factors is especially important in TC survivors. Whether BEP treatment increases CVD risk should be evaluated after more prolonged follow-up.
authors.affiliation: Department of Epidemiology, the Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Alexandra W
authors.initials: AW
authors.lastname: van den Belt-Dusebout
authors.forename: Janine
authors.initials: J
authors.lastname: Nuver
authors.forename: Ronald
authors.initials: R
authors.lastname: de Wit
authors.forename: Jourik A
authors.initials: JA
authors.lastname: Gietema
authors.forename: Wim W
authors.initials: WW
authors.lastname: ten Bokkel Huinink
authors.forename: Patrick T R
authors.initials: PT
authors.lastname: Rodrigus
authors.forename: Erik C
authors.initials: EC
authors.lastname: Schimmel
authors.forename: Berthe M P
authors.initials: BM
authors.lastname: Aleman
authors.forename: Flora E
authors.initials: FE
authors.lastname: van Leeuwen
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001761:Bleomycin / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D002945:Cisplatin / Q000009:adverse effects; D004407:Dysgerminoma / Q000188:drug therapy / Q000532:radiotherapy; D005047:Etoposide / Q000009:adverse effects; D006321:Heart / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D015994:Incidence; D008297:Male; D008482:Mediastinum / Q000528:radiation effects; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000139:chemically induced / Q000453:epidemiology* / Q000209:etiology*; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D018570:Risk Assessment; D018239:Seminoma / Q000188:drug therapy / Q000532:radiotherapy; D012907:Smoking / Q000009:adverse effects; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D014747:Vinblastine / Q000009:adverse effects
chemical_list: D001761:Bleomycin; D014747:Vinblastine; D005047:Etoposide; D002945:Cisplatin