Low-Dose Radiation Exposure and Circulatory Disease Risk by dfhrf555fcg


									type=editorial in-section=editorial id=litm710111 in-journal=bmj elocation-id=b4326
Exposure to radiation and higher risk of circulatory disease
Mark P Little
reader in statistics
    Department of Epidemiology and Public Health, Imperial College Faculty of Medicine,
    London W2 1PG
Research, doi:10.1136/bmj.b5349
Evidence is clear for high doses, but less so for lower doses
  The main risk to people directly exposed to low doses of ionising radiation is usually
assumed to be cancer. Various other effects (so called deterministic or tissue reaction effects)
are seen with exposure to high doses of radiation, such as in patients treated with
radiotherapy. In particular, various types of damage occur to the structures of the heart and to
the coronary, carotid, and other large arteries.(1) This damage is mainly caused by injury to
the microvasculature, partly as a result of excessive cell killing (for example, of capillary
cells) and the pro-inflammatory response to such damage, which leads to myocardial and
other ischaemia.(1)
     Evidence that an excess risk of cardiovascular disease occurs a long time after exposure to
lower doses of radiation has emerged from the Japanese atomic bomb survivor Life Span
Study (LSS) cohort(2)    (3)
                               and a few other groups.(4) (5) (6) (7) The linked cohort study by
Shimizu and colleagues (doi:10.1136/bmj.b5349)(8) adds six more years of follow-up (1998-
2003) to the previous analyses of the LSS mortality data,(2) and it concentrates entirely on
circulatory disease in the 86<thin>611 survivors.
     Shimizu and colleagues confirm previous reports of a significantly higher risk of heart
disease and stroke after exposure to radiation doses from 0 Gy to more than 3 Gy (86%
received <0.2 Gy).(8) The risks were slightly lower than those in the previous report, but this
may be because of the generally slightly higher individual dose estimates under the latest
(DS02) dosimetry compared with those used previously (DS86).
     A strength of the current study is that adjustment in a subsample of 36<thin>468 survivors
for sociodemographic factors (education, occupation), lifestyle factors (smoking, alcohol
intake), and health variables (obesity, diabetes) had little effect on the risks for any end point.
The LSS has several other strengths—the large population is probably representative of a
general population and the range of radiation doses was wide (0-3 Gy).
     Weaknesses include the possible selection of participants, certainly in the early years of
follow-up,(2) and their exposure to the privations of war and the immediate postwar period.

They were also subject to stress, which increases the risk of cardiovascular disease, although
the inverse relation between suicide and dose in the LSS suggests that, if anything, the dose-
response relation may be negatively biased.(9) A slightly worrying feature is that risks for
many non-malignant diseases in the LSS are increased to almost the same extent, suggesting
that the results may be biased.(2) Information on other well known risk factors for
cardiovascular disease, such as dietary cholesterol and physical activity is unavailable.
   Several recent reviews indicate that low doses of ionising radiation increase the risk of
cardiovascular disease in some groups exposed to radiation for medical and occupational
reasons, but significant heterogeneity exists.(7)     (10)
                                                             The possibility of confounding from well
known independent risk factors for circulatory disease (such as cigarette smoking, diabetes,
obesity, high blood pressure, and high concentrations of blood low density lipoprotein) and
other sources means that we cannot be sure that the associations are causal.(10)
   The mechanisms by which moderate doses of radiation received by the LSS survivors and
the low fractionated doses received by the occupationally exposed groups could cause
cardiovascular disease are unclear.(1)   (7) (10)
                                                    Inflammation is thought to be involved in most
stages of atherosclerotic disease, including its inception.(11) However, although we have
evidence for its involvement in the development of cardiovascular disease at high doses of
radiation,(1) the mechanism is unclear at low and moderate doses, particularly for
occupational exposure, where people receive on average much less than one electron track
per cell per day.(7)   (10)

   Shimizu and colleagues’ study adds to a growing body of evidence suggesting an
association between cardiovascular disease and exposure to low-moderate levels of radiation,
as well as the well known (and mechanistically well understood) association at high doses.(1)
However, statistical associations do not prove a causal association, and it is unclear whether
the biological mechanisms operating at high doses of radiation apply to low doses.(7)         (10)

Although new mechanisms for the effect of low dose radiation on the cardiovascular system
have been recently proposed,(12) they have yet to be experimentally tested. This should be the
focus of future research.

Competing interests: None declared.
Provenance and peer review: Commissioned; not externally peer reviewed.
   1 Schultz-Hector S, Trott KR. Radiation-induced cardiovascular diseases: is the
       epidemiologic evidence compatible with the radiobiologic data? Int J Radiat Oncol
       Biol Phys 2007; 67:10-8.

2 Preston DL, Shimizu Y, Pierce DA, Suyama A, Mabuchi K. Studies of mortality of
   atomic bomb survivors. Report 13: Solid cancer and noncancer disease mortality:
   1950-1997. Radiat Res 2003;160:381-407.
3 Yamada M, Wong FL, Fujiwara S, Akahoshi M, Suzuki G. Noncancer disease
   incidence in atomic bomb survivors, 1958-1998. Radiat Res 2004;161:622-32.
4 Ivanov VK, Maksioutov MA, Chekin SY, Petrov AV, Biryukov AP, Kruglova ZG, et al.
   The risk of radiation-induced cerebrovascular disease in Chernobyl emergency
   workers. Health Phys 2006;90:199-207.
5 Muirhead CR, O’Hagan JA, Haylock RG, Phillipson MA, Willcock T, Berridge GL, et
   al. Mortality and cancer incidence following occupational radiation exposure: third
   analysis of the National Registry for Radiation Workers. Br J Cancer 2009;100:206-
6 Azizova TV, Muirhead CR. Epidemiological evidence for circulatory diseases—
   occupational exposure. EU Scientific Seminar 2008. Emerging evidence for radiation
   induced circulatory diseases. Proceedings of a scientific seminar held in Luxembourg
   on 25 November 2008. Radiat Protect 2009;158:33-46.
7 Little MP, Tawn EJ, Tzoulaki I, Wakeford R, Hildebrandt G, Paris F, et al. A systematic
   review of epidemiological associations between low and moderate doses of ionizing
   radiation and late cardiovascular effects, and their possible mechanisms. Radiat Res
8 Shimizu Y, Kodama K, Nishi N, Kasagi F, Suyama A, Soda M, et al. Radiation
   exposure and circulatory disease risk: Hiroshima and Nagasaki atomic bomb survivor
   data, 1950-2003. BMJ 2010;340:b5349.
9 Shimizu Y, Pierce DA, Preston DL, Mabuchi K. Studies of the mortality of atomic
   bomb survivors. Report 12, part II. Noncancer mortality: 1950-1990. Radiat Res
10 Little MP, Tawn EJ, Tzoulaki I, Wakeford R, Hildebrandt G, Paris F, et al. Review and
   meta-analysis of epidemiological associations between low/moderate doses of ionizing
   radiation and circulatory disease risks, and their possible mechanisms. Radiat Environ
   Biophys (in press); doi:10.1007/s00411-009-0250-z.
11 Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J
   Med 2005;352:1685-95.

  12 Little MP, Gola A, Tzoulaki I. A model of cardiovascular disease giving a plausible
     mechanism for the effect of fractionated low-dose ionizing radiation exposure. PLoS
     Comput Biol 2009;5:e1000539.

Cite this as: BMJ 2010;340:b4326


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