title: Cardiovascular status of childhood cancer survivors exposed and unexposed to cardiotoxic therapy.
abstract: OBJECTIVE
  To determine whether cardiovascular abnormalities in childhood cancer survivors are restricted to patients exposed to cardiotoxic anthracyclines and cardiac irradiation and how risk factors for atherosclerotic disease and systemic inflammation contribute to global cardiovascular status.
  
  
  METHODS
  We assessed echocardiographic characteristics and atherosclerotic disease risk in 201 survivors of childhood cancer with and without exposure to cardiotoxic treatments at a median of 11 years after diagnosis (range, 3 to 32 years) and in 76 sibling controls.
  
  
  RESULTS
  The 156 exposed survivors had below normal left ventricular (LV) mass, wall thickness, contractility, and fractional shortening and above normal LV afterload. The 45 unexposed survivors also had below normal LV mass overall, and females had below normal LV wall thickness. Exposed and unexposed survivors, compared with siblings, had higher levels of N-terminal pro-brain natriuretic peptide (81.7 and 69.0 pg/mL, respectively, v 39.4 pg/mL), higher mean fasting serum levels of non-high-density lipoprotein cholesterol (126.5 and 121.1 mg/dL, respectively, v 109.8 mg/dL), higher insulin levels (10.4 and 10.5 μU/mL, respectively, v 8.2 μU/mL), and higher levels of high-sensitivity C-reactive protein (2.7 and 3.1 mg/L, respectively, v 0.9 mg/L; P < .001 for all comparisons). Age-adjusted, predicted-to-ideal 30-year risk of myocardial infarction, stroke, or coronary death was also higher for exposed and unexposed survivors compared with siblings (2.16 and 2.12, respectively, v 1.70; P < .01 for both comparisons).
  
  
  CONCLUSIONS
  Childhood cancer survivors not receiving cardiotoxic treatments nevertheless have cardiovascular abnormalities, systemic inflammation, and an increased risk of atherosclerotic disease. Survivorship guidelines should address cardiovascular concerns, including the risk of atherosclerotic disease and systemic inflammation, in exposed and unexposed survivors.
authors.affiliation: University of Miami Miller School of Medicine, Miami, FL 33101, USA. slipshultz@med.miami.edu
authors.forename: Steven E
authors.initials: SE
authors.lastname: Lipshultz
authors.forename: David C
authors.initials: DC
authors.lastname: Landy
authors.forename: Gabriela
authors.initials: G
authors.lastname: Lopez-Mitnik
authors.forename: Stuart R
authors.initials: SR
authors.lastname: Lipsitz
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Hinkle
authors.forename: Louis S
authors.initials: LS
authors.lastname: Constine
authors.forename: Carol A
authors.initials: CA
authors.lastname: French
authors.forename: Amy M
authors.initials: AM
authors.lastname: Rovitelli
authors.forename: Cindy
authors.initials: C
authors.lastname: Proukou
authors.forename: M Jacob
authors.initials: MJ
authors.lastname: Adams
authors.forename: Tracie L
authors.initials: TL
authors.lastname: Miller
mesh_terms: D000293:Adolescent; D000328:Adult; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood; D003324:Coronary Artery Disease / Q000139:chemically induced / Q000453:epidemiology; D004452:Echocardiography; D005260:Female; D006331:Heart Diseases / Q000097:blood / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009369:Neoplasms / Q000188:drug therapy*; D010446:Peptide Fragments / Q000097:blood; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D035781:Siblings; D017741:Survivors / Q000706:statistics & numerical data; D013997:Time Factors
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein; D002784:Cholesterol