RERF Report No. 15-15

Paper published in Radiation Research§“Heart disease mortality in the Life Span Study, 1950-2008”
Ikuno Takahashi, Yukiko Shimizu, Eric J. Grant, John Cologne, Kotaro Ozasa, Kazunori Kodama
Radiat Res.2017 (March); 187(3):319-32(doi: 10.1667/RR14347.1)
Study Findings
Radiation risks for heart disease mortality in the Life Span Study (LSS) were heterogeneous among
subtypes, indicating possible differences in radiation-related pathogenesis among the subtypes. Inaddition, time-dependent changes in heart disease mortality in Japan during the long observational
period may have also impacted risk analysis.
Explanation
With regard to radiation risks for heart disease mortality among the LSS population during theperiod from 1950 through 2008, we conducted analyses of heart-disease subtypes over different time
periods.
1. Study Purpose
The Radiation Effects Research Foundation’s follow-up of atomic bomb survivors for theobservation period 1950–2003 reported that total body irradiation at dose levels of 0.5–1.0 Gy or
higher could be responsible for increased rates of mortality from heart disease. Heart disease consistsof four major subtypes (ischemic heart disease [IHD], valvular heart disease [VHD], hypertensive
organ damage [HOD], and heart failure [HF])*, each of which has distinctive pathogenesis,
mechanisms, and risk factors. In addition, subtype-specific mortality rates in Japan changed greatly
after World War II. Consequently, it has become essential to review radiation effects according to heartdisease subtype and to examine the effects of subtype-specific trends in mortality rates in Japan on theestimation of dose response among the LSS cohort. We addressed this factor by analyzing the dose
response of A-bomb radiation exposure by heart disease subtype over different time periods andevaluating radiation effects.

*Ischemic heart disease (IHD): arteriosclerotic disease, with high incidence and mortality rates
around the world
Valvular heart disease (VHD): disease characterized by damage to or a defect in heart
valve(s), caused by after-effects of infection (rheumatic) and age-related/arteriosclerotic
degeneration of valve(s) (non-rheumatic)
Hypertensive organ damage (HOD): hypertension-associated dysfunction of the heart orkidney
Heart failure (HF): dysfunction of the heart due to any heart disease
2. Study Methods
We estimated excess relative risk (ERR)* for heart disease mortality after A-bomb radiation
exposure among 86,600 LSS subjects. Based on differences in pathogenesis and related mechanisms,
heart disease cases were classified into the aforementioned four subtypes. Taking into accountdramatic progress in the quality of medical diagnostic techniques, as well as changes in the coding
rules for the International Classification of Diseases (ICD), the total observation period (1950-2008)
was divided into four periods: 1950–68, 1969–80, 1981–94, and 1995–2008.
*Excess relative risk: Excess relative risk (ERR) is expressed as relative risk (RR) minus one, or that
portion of the total RR accounted for by radiation exposure. RR is the ratio of the risk in an exposed
population to that in a comparable unexposed population.

RERF Report No. 15-15

3. Study Results
1) For the entire observation period, significant increases in ERR were observed for VHD, HOD, andHF (ERR/Gy = 0.45, 0.36, 0.21, respectively), and ERR for heart disease was 0.14, showing linear
dose-response relationships. However, these relationships reflected dose response mainly in thehigh-dose range: ERR for all heart diseases was statistically significant in the dose range of 0–0.7
Gy and higher. No significant association between radiation exposure and IHD was observed.
2) Assessment of specific time periods revealed significant dose responses for HOD and rheumatic
VHD in the early period (1950–68), and a significant increase in ERR for non-rheumatic VHS in
the recent period (1995–2008).
Study SignificanceAs was the case in a previous report for the period 1950–2003, the present study revealed
significant increases in radiation risk for heart disease mortality among the LSS cohort from 1950 to2008, but review of specific subtypes of heart disease indicated different trends in association withradiation dose. Subtype-specific review also showed that the significance of dose response differedamong the four observation periods, suggesting the possibility that general trends in subtype-specificheart disease mortality in Japan during the long observation period may have impacted risk estimation.
The Radiation Effects Research Foundation has studied A-bomb survivors and their offspring in Hiroshima
and Nagasaki for around 70 years. RERF’s research achievements are considered the principal scientific basis forradiation risk assessment by the United Nations Scientific Committee on the Effects of Atomic Radiation(UNSCEAR) and for recommendations regarding radiation protection standards by the International
Commission on Radiological Protection (ICRP). RERF expresses its profound gratitude to the A-bomb survivors
and survivors’ offspring for their cooperation in our studies.

§Radiation Research, which is an official monthly journal of the Radiation Research Society, publishes
original peer-reviewed papers and review articles on radiation effects and related issues in the fields ofphysics, chemistry, biology, and medicine. (Impact factor in 2015: 2.67)