title: Modifiable risk factors and major cardiac events among adult survivors of childhood cancer.
abstract: OBJECTIVE
  To evaluate the relative contribution of modifiable cardiovascular risk factors on the development of major cardiac events in aging adult survivors of childhood cancer.
  
  
  METHODS
  Among 10,724 5-year survivors (median age, 33.7 years) and 3,159 siblings in the Childhood Cancer Survivor Study, the prevalence of hypertension, diabetes mellitus, dyslipidemia, and obesity was determined, along with the incidence and severity of major cardiac events such as coronary artery disease, heart failure, valvular disease, and arrhythmia. On longitudinal follow-up, rate ratios (RRs) of subsequent cardiac events associated with cardiovascular risk factors and cardiotoxic therapy were assessed in multivariable Poisson regression models.
  
  
  RESULTS
  Among survivors, the cumulative incidence of coronary artery disease, heart failure, valvular disease, and arrhythmia by 45 years of age was 5.3%, 4.8%, 1.5%, and 1.3%, respectively. Two or more cardiovascular risk factors were reported by 10.3% of survivors and 7.9% of siblings. The risk for each cardiac event increased with increasing number of cardiovascular risk factors (all P(trend) < .001). Hypertension significantly increased risk for coronary artery disease (RR, 6.1), heart failure (RR, 19.4), valvular disease (RR, 13.6), and arrhythmia (RR, 6.0; all P values < .01). The combined effect of chest-directed radiotherapy plus hypertension resulted in potentiation of risk for each of the major cardiac events beyond that anticipated on the basis of an additive expectation. Hypertension was independently associated with risk of cardiac death (RR, 5.6; 95% CI, 3.2 to 9.7).
  
  
  CONCLUSIONS
  Modifiable cardiovascular risk factors, particularly hypertension, potentiate therapy-associated risk for major cardiac events in this population and should be the focus of future interventional studies.
authors.affiliation: Gregory T. Armstrong, Daniel A. Mulrooney, and Leslie L. Robison, St. Jude Children's Research Hospital, Memphis, TN; Kevin C. Oeffinger and Charles A. Sklar, Memorial Sloan-Kettering Cancer Center, New York, NY; Yan Chen and Yutaka Yasui, University of Alberta, Edmonton, Alberta, Canada; Toana Kawashima, Wendy Leisenring, and Eric J. Chow, Fred Hutchinson Cancer Research Center; Eric J. Chow, Seattle Children's Hospital, Seattle, WA; Marilyn Stovall and Jean-Bernard Durand, The University of Texas MD Anderson Cancer Center, Houston, TX; and Ann C. Mertens, William Border, and Lillian R. Meacham, Emory University, Atlanta, GA.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Armstrong
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Oeffinger
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Toana
authors.initials: T
authors.lastname: Kawashima
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasui
authors.forename: Wendy
authors.initials: W
authors.lastname: Leisenring
authors.forename: Marilyn
authors.initials: M
authors.lastname: Stovall
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Chow
authors.forename: Charles A
authors.initials: CA
authors.lastname: Sklar
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Mulrooney
authors.forename: Ann C
authors.initials: AC
authors.lastname: Mertens
authors.forename: William
authors.initials: W
authors.lastname: Border
authors.forename: Jean-Bernard
authors.initials: JB
authors.lastname: Durand
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
authors.forename: Lillian R
authors.initials: LR
authors.lastname: Meacham
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D006331:Heart Diseases / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000401:mortality*; D016012:Poisson Distribution; D012307:Risk Factors; D017741:Survivors