Association between radiation, glaucoma subtype, and retinal vessel diameter in atomic bomb survivors.

We examined the relationship between glaucoma subtype and retinal vascular caliber as markers of ocular circulation. Subjects were Japanese atomic bomb survivors in Hiroshima and Nagasaki. After a screening examination, potential cases were subjected to further definitive examination. The diameters of central retinal artery and vein equivalents (CRAE and CRVE) on digitized retinal photographs were measured using an established method. Generalized linear regression analyses were used to examine the associations among vessel diameters, radiation exposure, and prevalence of glaucoma subtypes among the study subjects. We identified 196 cases of glaucoma (12%) based on optic disc appearance, perimetry results, and other ocular findings. The main subtypes were primary angle-closure glaucoma, primary open-angle glaucoma and normal-tension glaucoma (NTG). NTG was the dominant subtype (78%). NTG was negatively associated with CRAE and CRVE, and positively associated with radiation dose. CRVE was negatively associated with radiation dose and the association was unclear for CRAE. The smaller retinal vessel caliber in NTG patients than in subjects without glaucoma may indicate an association between ocular blood flow and the pathogenesis of NTG. However, significant relationships among vessel calibers, NTG and radiation exposure were not clear.

Association of Weight Fluctuation With Mortality in Japanese Adults.

Importance: Weight cycling is associated with the risk of mortality from heart disease, but many studies have not distinguished between simple nonlinear (monotone) weight changes and more complex changes that reflect fluctuations. Objective: To assess whether extreme body weight variation is associated with mortality after controlling for nonlinear weight changes. Design, Setting, and Participants: In this prospective clinical cohort study, 4796 Japanese atomic bomb survivors were examined in the clinic as part of a biennial health examination and research program. The study consisted of a 20-year longitudinal baseline period (July 1, 1958, to June 30, 1978) and subsequent mortality follow-up of 27 years (July 1, 1978, to June 30, 2005) Participants were initially between the ages of 20 and 49 years during the baseline period and, throughout the baseline period, had no diagnoses of cardiovascular disease (CVD) or cancer and attended at least 7 of 10 scheduled examinations. Data analysis was performed from October 16, 2015, to May 13, 2016. Exposures: Residual variability in body mass index (BMI) during the baseline period. Main Outcomes and Measures: Outcomes were mortality from ischemic heart disease, cerebrovascular disease, other CVDs combined, other causes (except cancer), and cancer. Root mean squared error was calculated to capture individual residual variation in BMI after adjustment for baseline BMI trends, and the association of magnitude of residual variation with mortality was calculated as relative risk. Results: In total, 4796 persons (mean [SD] age, 35.0 [7.3] years at first baseline examination; 3252 [67.8%] female; mean [SD] BMI, 21.2 [2.8] at first baseline visit [20.6 (2.4) among men and 21.5 (2.9) among women]) participated in the study. During follow-up, 1550 participants died: 82 (5.3% of all deaths) of ischemic heart disease, 181 (11.7%) of cerebrovascular disease, 186 (12.0%) of other CVDs, 615 (39.7%) of cancer, and 486 (31.3%) of other causes. Magnitude of residual variation in weight was associated with all-cause mortality (relative risk, 1.25 for 1 U of additional variation; 95% CI, 1.06-1.47) and ischemic heart disease mortality (relative risk, 2.49; 95% CI, 1.41-4.38). Conclusions and Relevance: The findings suggest that an association exists between weight variation and heart disease mortality and that weight loss interventions, if deemed to be necessary, should be considered carefully.

Association Between Prevalence of Peripheral Artery Disease and Radiation Exposure in the Atomic Bomb Survivors.

Background Past reports suggested that total-body irradiation at 0.5 to 1.0 Gy could be responsible for atherosclerosis. Peripheral artery disease ( PAD ) is a manifestation of systematic atherosclerosis. Whether the consequences of a low-to-moderate dose of radiation include increased risk of PAD remains to be determined. The purpose of this study was to examine the association between radiation exposure and prevalence of PAD among Japanese atomic bomb survivors. Methods and Results Radiation exposure from the atomic bombing was assessed in 3476 participants (41.1% men, mean age 74.8 years with SD 6.4 years) with a cross-sectional survey in 2010 to 2014. Left- and right-side ankle-brachial indexes and upstroke time ( UT ) were obtained using oscillometric VP -2000. PAD was defined as an ankle-brachial index of 1.0 or less or a prior history related to revascularization. UT was considered a sensitive marker of early-stage PAD . Association between radiation exposure and PAD or UT was assessed using multivariable regression analyses with adjustment for potential confounding factors. Of 3476 participants, 79 (2.3%) were identified as having prevalent PAD . Multivariate logistic regression analysis indicated that radiation dose was unrelated to PAD prevalence (odds ratio, 0.83; 95% confidence interval [0.57-1.21]). UT appeared to increase with radiation dose, but the increase was not statistically significant (1.09 ms/Gy; 95% confidence interval [-0.17 to 2.36]). Conclusions We found no clear association of radiation dose with PAD , but it remains to be determined whether UT is associated with radiation dose.

Thyroid Dysfunction and Autoimmune Thyroid Diseases Among Atomic Bomb Survivors Exposed in Childhood.

Context: The risk of thyroid cancer increases and persists for decades among individuals exposed to ionizing radiation in childhood, although the long-term effects of childhood exposure to medium to low doses of radiation on thyroid dysfunction and autoimmune thyroid diseases have remained unclear. Objective: To evaluate radiation dose responses for the prevalence of thyroid dysfunction and autoimmune thyroid disease among atomic bomb survivors exposed in childhood. Design, Setting, and Participants: Hiroshima and Nagasaki atomic bomb survivors who were younger than 10 years old at exposure underwent thyroid examinations at the Radiation Effects Research Foundation between 2007 and 2011, which was 62 to 66 years after the bombing. Data from 2668 participants (mean age, 68.2 years; 1455 women) with known atomic bomb thyroid radiation doses (mean dose, 0.182 Gy; dose range, 0 to 4.040 Gy) were analyzed. Main Outcome and Measures: Dose-response relationships between atomic bomb radiation dose and the prevalence of hypothyroidism, hyperthyroidism (Graves' disease), and positive for antithyroid antibodies. Results: Prevalences were determined for hypothyroidism (129 cases, 7.8%), hyperthyroidism (32 cases of Graves' disease, 1.2%), and positive for antithyroid antibodies (573 cases, 21.5%). None of these was associated with thyroid radiation dose. Neither thyroid antibody-positive nor -negative hypothyroidism was associated with thyroid radiation dose. Additional analyses using alternative definitions of hypothyroidism and hyperthyroidism found that radiation dose responses were not significant. Conclusions: Radiation effects on thyroid dysfunction and autoimmune thyroid diseases were not observed among atomic bomb survivors exposed in childhood, at 62 to 66 years earlier. The cross-sectional design and survival bias were limitations of this study.

Cardiovascular disease among atomic bomb survivors.

PURPOSE: The profile of cardiovascular disease in Japan has been different from that in Western countries. Hypertension was the major cause not only for hemorrhagic stroke but also for ischemic stroke and heart disease in the past, and the influence of hypertension has decreased with calendar years because of reduced salt intake and westernization of lifestyle, and also improved medical care. The health status of atomic bomb survivors has reflected this profile as well as radiation effects. It is also likely that this cohort has been affected by the difficult conditions experienced in the aftermath of the war and atomic bombings. In this article, we tried to make a consistent interpretation of epidemiological findings of atomic bomb radiation effects on cardiovascular disease. CONCLUSION: Among the atomic bomb survivors, radiation exposure was associated with some cardiovascular diseases that are often associated with hypertension, and dose response appeared to be primarily non-linear among those who were exposed at younger ages. These effects are thought to reflect the nature of whole body irradiation. But, some findings remain inconsistent, possibly because of possible misclassification in death certificate diagnoses in the Life Span Study as well as selected information from the Adult Health Study which was limited to participants, focused on specific outcomes, and gathered in selected periods of follow-up. Therefore, a comprehensive and balanced interpretation of the results from both groups is necessary.

Heart Disease Mortality in the Life Span Study, 1950-2008.

Based on the findings from the Radiation Effects Research Foundation's studies of the cohort of Japanese atomic bomb survivors, it has been reported that total-body irradiation at 0.5-1.0 Gy could be responsible for increased rates of mortality from broad-based categories of cardiovascular disease (CVD), i.e., stroke and heart disease. However, CVD consists of various subtypes that have potentially different radiation dose responses, as well as subtype-specific risks that have not been fully evaluated. Potential problems with changes in the coding rules for the International Classification of Diseases (ICD) and the underlying causes and trends in CVD mortality in Japan also need to be considered. The goal of this study was to clarify the radiation risk of subtype-specific heart disease over different time periods. Radiation dose response was examined for mortality from several heart disease subtypes in 86,600 members of the Life Span Study (LSS) cohort during 1950-2008. These subtypes included ischemic heart disease (IHD), valvular heart disease (VHD), hypertensive organ damage (HOD) and heart failure (HF). Individual radiation doses ranged between 0 and 4 Gy. In addition to analyses for the total period, we examined specific periods, 1950-1968, 1969-1980, 1981-1994 and 1995-2008, corresponding to major developments in medical technologies and ICD code revisions. We observed significant positive associations between radiation dose and mortality from heart disease overall in 1950-2008 [excess relative risk or ERR/Gy (95% CI) = 0.14 (0.06, 0.22)]. Subtype-specific ERRs also positively increased with dose: 0.45 (0.13, 0.85) for VHD, 0.36 (0.10, 0.68) for HOD and 0.21 (0.07, 0.37) for HF, respectively. No significant departure from linearity was shown for the dose-response model. Although there was no evidence for a threshold in a model function, the lowest dose ranges with a statistically significant dose response were 0-0.7 Gy for heart disease overall and VHD, 0-1.5 Gy for HOD and 0-0.4 Gy for HF. No significant association between radiation exposure and IHD was observed in any model, although a quadratic model fit the best. The risk of HOD and rheumatic VHD increased significantly in the earliest periods [ERR/Gy = 0.59 (0.07, 1.32) and 1.34 (0.24, 3.16), respectively]. The risk of nonrheumatic VHD increased with calendar time and was significant in the latest period [ERR/Gy = 0.75 (0.02, 1.92)]. The risk of IHD, especially for myocardial infarction, tended to be elevated in the most recent period after 2001, where cautious interpretation is needed due to the uncertain validity of death diagnosis. Radiation risks of heart disease mortality in the LSS appeared to vary substantially among subtypes, indicating possible differences in radiation-induced pathogenesis. Trends in CVD rates in Japan during the long observation period may also impact risk analyses.

Mortality Analysis of the Life Span Study (LSS) Cohort Taking into Account Multiple Causes of Death Indicated in Death Certificates.

Mortality analyses have been performed using underlying causes of death as reported on death certificates; these are uniquely determined for a deceased person according to the World Health Organization coding system. Comorbidities, the disease conditions other than the underlying cause of death from death certificates recording multiple causes of death, have rarely been explored in Life Span Study subjects. The purpose of this study was to clarify associations between atomic bomb radiation exposure and mortality from combinations of the underlying cause of death and comorbidities. The focused follow-up period was 1977-2003, prior to which death certificate accuracy was unreliable. The study cohort was comprised of 10,017 people for whom the category "all circulatory disease" was listed as the underlying cause of death, of which heart disease (rheumatic, hypertensive and ischemic heart disease) and stroke were major subtypes. Comorbidities considered were pneumonia, renal disease, diabetes mellitus, cancer and the major circulatory disease subtypes listed above. Poisson regression models were used for analyses. Excess relative risks (ERRs) for mortality at 1 Gy were significantly increased when cancer was comorbid with all circulatory disease, heart disease, ischemic heart disease or stroke, ranging from 0.61 [95% confidence interval (CI): 0.13, 1.41; N = 177] for all circulatory diseases to 1.60 (CI: 0.07, 4.86; N = 42) for ischemic heart disease. Among the other comorbidities, only diabetes comorbid with heart disease had a significant radiation dose response (ERR at 1 Gy of 0.62, CI: 0.10, 1.46; N = 128). It remains uncertain if the high ERRs with comorbid cancers were anomalous due to the small number of cases or some dissimilarity in statistical methodologies, or if this might suggest some pathogenetic basis for increased fatality. For this reason, further investigation is required.

Prognostic Significance of Premature Ventricular Contractions without Obvious Heart Diseases Determined by Standard 12-Lead Electrocardiography Considering their Morphology.

BACKGROUND: Although ventricular premature contraction (VPC) commonly arises in subjects with and without heart diseases, the prognosis of VPC has remained controversial and the effect of their morphology on mortality has not been fully determined in subjects without obvious heart diseases. The objective of this study was to assess the morphologic effect of VPC on mortality. METHODS: Japanese atomic bomb survivors (n = 6685) underwent baseline health examinations and standard 12-lead electrocardiogram (ECG) between January 1990 and December 1991. Of these, we extracted data from 5,685 (67.1% women) subjects who had neither heart diseases nor electrocardiographic abnormalities at baseline. Among them, we identified 131 VPC cases using standard 12-lead ECG and classified them into left bundle branch block (LBBB) type (n = 74), right bundle branch block (RBBB) type (n = 21), and undetermined type (n = 36) according to their morphology. These subjects were followed up until December 2008; we compared all-cause, cardiac and coronary heart disease (CHD) mortality rates using multivariate Cox regression analysis between those with and without VPC. RESULTS: No VPCs were associated with all-cause and cardiac mortality, but the LBBB type was significantly associated with CHD mortality (hazard ratio, 2.73; 95% confidence interval, 1.11-6.73) after controlling for age, sex, smoking status, alcohol consumption, and underlying diseases. CONCLUSIONS: Among Japanese atomic bomb survivors without obvious heart diseases, LBBB-type VPC was associated with increased CHD mortality. Larger studies are needed to confirm the effect of morphology as it might help to predict the risk.

Risk of death among children of atomic bomb survivors after 62 years of follow-up: a cohort study.

BACKGROUND: No clear epidemiological hereditary effects of radiation exposure in human beings have been reported. However, no previous studies have investigated mortality into middle age in a population whose parents were exposed to substantial amounts of radiation before conception. We assessed mortality in children of the atomic bomb survivors after 62 years of follow-up. METHODS: In this prospective cohort study, we assessed 75 327 singleton children of atomic bomb survivors in Hiroshima and Nagasaki and unexposed controls, born between 1946 and 1984, and followed up to Dec 31, 2009. Parental gonadal doses of radiation from the atomic bombings were the primary exposures. The primary endpoint was death due to cancer or non-cancer disease, based on death certificates. FINDINGS: Median follow-up was 54·3 years (IQR 45·4-59·3). 5183 participants died from disease. The mean age of the 68 689 surviving children at the end of follow-up was 53·1 years (SD 7·9) with 15 623 (23%) older than age 60 years. For parents who were exposed to a non-zero gonadal dose of radiation, the mean dose was 264 mGy (SD 463). We detected no association between maternal gonadal radiation exposure and risk of death caused by cancer (hazard ratio [HR] for 1 Gy change in exposure 0·891 [95% CI 0·693-1·145]; p=0·36) or risk of death caused by non-cancer diseases (0·973 [0·849-1·115]; p=0·69). Likewise, paternal exposure had no effect on deaths caused by cancer (0·815 [0·614-1·083]; p=0·14) or deaths caused by non-cancer disease (1·103 [0·979-1·241]; p=0·12). Age or time between parental exposure and delivery had no effect on risk of death. INTERPRETATION: Late effects of ionising radiation exposure include increased mortality risks, and models of the transgenerational effects of radiation exposure predict more genetic disease in the children of people exposed to radiation. However, children of people exposed to the atomic bombs in Hiroshima and Nagasaki had no indications of deleterious health effects after 62 years. Epidemiological studies complemented by sensitive molecular techniques are needed to understand the overall effects of preconception exposure to ionising radiation on human beings.

Exposure to Atomic Bomb Radiation and Age-Related Macular Degeneration in Later Life: The Hiroshima-Nagasaki Atomic Bomb Survivor Study.

PURPOSE: To investigate the association between radiation exposure from the atomic bombings and the prevalence of age-related macular degeneration (AMD) among older residents of Hiroshima and Nagasaki. METHODS: The Adult Health Study is a cohort study of atomic bomb survivors living in Hiroshima and Nagasaki, comprising 2153 participants who underwent examinations with retinal fundus photographs in 2006-2008. The radiation dose to the eye for the analysis was estimated with the revised dosimetry system (DS02). The retinal photographs were graded according to the Wisconsin Age-Related Maculopathy Grading System modified for nonstereoscopic retinal images. Early and late AMD were defined according to the type of lesion detected in the worse eye of the participants. Person-specific data were analyzed by using a logistic regression model to assess the association between radiation dose and AMD. RESULTS: Among the 1824 subjects with gradable retinal images (84.7% of the overall participants), the estimated eye dose was widely distributed, with a mean of 0.45 Gy and standard deviation of 0.74 Gy. The prevalence of early and late AMD was 10.5% and 0.3%, respectively. There were no significant associations between radiation dose and AMD, with each 1-Gy increase in exposure, adjusted odds ratio was 0.93 (95% confidence interval [CI], 0.75-1.15) for early AMD and 0.79 (95% CI, 0.21-2.94) for late AMD. CONCLUSIONS: No significant associations were found between atomic bomb irradiation early in life and the prevalence of early or late AMD later in life among Japanese atomic bomb survivors.

Association of radiation dose with prevalence of thyroid nodules among atomic bomb survivors exposed in childhood (2007-2011).

IMPORTANCE: Few studies have evaluated the association of radiation dose with thyroid nodules among adults exposed to radiation in childhood. OBJECTIVE: To evaluate radiation dose responses on the prevalence of thyroid nodules in atomic bomb survivors exposed in childhood. DESIGN, SETTING, AND PARTICIPANTS: This survey study investigated 3087 Hiroshima and Nagasaki atomic bomb survivors who were younger than 10 years at exposure and participated in the thyroid study of the Adult Health Study at the Radiation Effects Research Foundation. Thyroid examinations including thyroid ultrasonography were conducted between October 2007 and October 2011, and solid nodules underwent fine-needle aspiration biopsy. Data from 2668 participants (86.4% of the total participants; mean age, 68.2 years; 1213 men; and 1455 women) with known atomic bomb thyroid radiation doses (mean dose, 0.182 Gy; median dose, 0.018 Gy; dose range, 0-4.040 Gy) were analyzed. MAIN OUTCOMES AND MEASURES: The prevalence of all thyroid nodules having a diameter of 10 mm or more (consisting of solid nodules [malignant and benign] and cysts), prevalence of small thyroid nodules that were less than 10 mm in diameter detected by ultrasonography, and atomic bomb radiation dose-responses. RESULTS: Thyroid nodules with a diameter of 10 mm or more were identified in 470 participants (17.6%): solid nodules (427 cases [16.0%]), malignant tumors (47 cases [1.8%]), benign nodules (186 cases [7.0%]), and cysts (49 cases [1.8%]), and all were significantly associated with thyroid radiation dose. Excess odds ratios per gray unit were 1.65 (95% CI, 0.89-2.64) for all nodules, 1.72 (95% CI, 0.93-2.75) for solid nodules, 4.40 (95% CI, 1.75-9.97) for malignant tumors, 2.07 (95% CI, 1.16-3.39) for benign nodules, and 1.11 (95% CI, 0.15-3.12) for cysts. The interaction between age at exposure and the dose was significant for the prevalence of all nodules (P = .003) and solid nodules (P < .001), indicating that dose effects were significantly higher with earlier childhood exposure. No interactions were seen for sex, family history of thyroid disease, antithyroid antibodies, or seaweed intake. No dose-response relationships were observed for small (<10-mm diameter) thyroid nodules. CONCLUSIONS AND RELEVANCE: Radiation effects on thyroid nodules exist in atomic bomb survivors 62 to 66 years after their exposure in childhood. However, radiation exposure is not associated with small thyroid nodules.

Prevalence, incidence and progression of lumbar spondylosis by gender and age strata.

OBJECTIVES: To identify the prevalence, incidence and progression of radiographic lumbar spondylosis (LS). METHODS: From the Adult Health Study conducted by the Radiation Effects Research Foundation, 1,204 participants aged 44-85 years who had lumbar spine radiographs in 1990-1992 were reexamined in 1998-2000 (mean 7.9-year interval). The radiographic severity of LS was determined by Kellgren/Lawrence (KL) grading. RESULTS: In the overall population, the prevalence of radiographic KL ≥ 2 and ≥ 3 LS was 52.9% and 23.6%, respectively. KL ≥ 2 LS was more prevalent in men, whereas KL ≥ 3 LS was more prevalent in women. During the 8-year follow-up, the incidence of KL ≥ 2 LS in men and women was 65.5% and 46.6%, that of KL ≥ 3 LS was 27.3% and 29.5%, that of progressive LS was 31.3% and 34.0%, and multilevel LS was 44.9% and 33.4%, respectively. Body-mass index was a risk factor for both KL ≥ 2 and KL ≥ 3 LS, after adjusting for age and sex. CONCLUSIONS: The present longitudinal study revealed the prevalence, incidence and progression of radiographic LS. Prevalence and incidence of KL ≥ 2 LS was higher in men than women, while, those of KL ≥ 3 were similar between men and women.

Is the association between smoking and the retinal venular diameter reversible following smoking cessation?

PURPOSE: Wider retinal venular caliber is shown to be associated with an increased risk of stroke, and smoking is associated with a wider retinal venular caliber. However, the impact of smoking cessation on the retinal vessels has not been previously reported. We examined this issue in an adult cohort of atomic bomb survivors. METHODS: In the Adult Health Study of Japanese atomic bomb survivors, 1664 subjects had retinal photographs taken from 2006 to 2008. The central retinal artery and vein equivalents (CRAE and CRVE) were calculated using a semiautomated software program. Multiple surveys have assessed the effects of smoking since 1963. The associations between smoking, the time since cessation, and the retinal vessel caliber were determined using linear mixed effects models. RESULTS: The CRVE was associated with an increased number of cigarettes smoked per day among women after adjusting for potential confounding factors (age, sex, blood pressure, hypertensive medications, white blood cell count, diabetes, body mass index, lipids, and radiation dose). Females who smoked 10 cigarettes per day had a 6.9-µm wider mean CRVE (P = 0.001) than nonsmokers. Females who had stopped smoking for 10 or more years had a mean CRVE similar to those who had never smoked (191.8 vs. 194.4 µm; P = 0.23). These associations were not observed in males or for CRAE. CONCLUSIONS: Wider retinal venular caliber is associated with smoking in Japanese females; however, this association becomes nonsignificant after 10 or more years of smoking cessation, suggesting that the impact of smoking on retinal venular dilation is reversible following long-term smoking cessation.

A report from the 2013 international workshop: radiation and cardiovascular disease, Hiroshima, Japan.

Two longitudinal cohort studies of Japanese atomic bomb survivors-the life span study (LSS) and the adult health study (AHS)-from the Radiation Effects Research Foundation (RERF) indicate that total body irradiation doses less than 1 Gy are associated with an increased risk of cardiovascular disease (CVD), but several questions about this association remain.In particular, the diversity of heart disease subtypes and the high prevalence of other risk factors complicate the estimates of radiation effects. Subtype-specific analyses with more reliable diagnostic criteria and measurement techniques are needed. The radiation effects on CVD risk are probably tissue-reaction (deterministic) effects, so the dose-response relationships for various subtypes of CVD may be nonlinear and therefore should be explored with several types of statistical models.Subpopulations at high risk need to be identified because effects at lower radiation doses may occur primarily in these susceptible subpopulations. Whether other CVD risk factors modify radiation effects also needs to be determined. Finally, background rates for various subtypes of CVD have historically differed substantially between Japanese and Western populations, so the generalisability to other populations needs to be examined.Cardiovascular disease mechanisms and manifestations may differ between high-dose local irradiation and low-dose total body irradiation (TBI)-microvascular damage and altered metabolism from low-dose TBI, but coronary artery atherosclerosis and thrombotic myocardial infarcts at high localised doses. For TBI, doses to organs other than the heart may be important in pathogenesis of CVD, so data on renal and liver disorders, plaque instability, microvascular damage, metabolic disorders, hypertension and various CVD biomarkers and risk factors are needed. Epidemiological, clinical and experimental studies at doses of less than 1 Gy are necessary to clarify the effects of radiation on CVD risk.

Radiation exposure and the risk of mortality from noncancer respiratory diseases in the life span study, 1950-2005.

An apparent association between radiation exposure and noncancer respiratory diseases (NCRD) in the Life Span Study (LSS) of atomic bomb survivors has been reported, but the biological validity of that observation is uncertain. This study investigated the possibility of radiation causation of noncancer respiratory diseases in detail by examining subtypes of noncancer respiratory diseases, temporal associations, and the potential for misdiagnosis and other confounding factors. A total of 5,515 NCRD diagnoses listed as the underlying cause of death on the death certificate were observed among the 86,611 LSS subjects with estimated weighted absorbed lung doses. Radiation dose-response analyses were conducted using Cox proportional hazard regression for pneumonia/influenza, other acute respiratory infections, chronic obstructive pulmonary disease and asthma. The linear excess relative risks (ERR) per gray (Gy) were 0.17 (95% CI 0.08, 0.27) for all NCRD and 0.20 (CI 0.09, 0.34) for pneumonia/influenza, which accounted for 63% of noncancer respiratory disease deaths. Adjustments for lifestyle and sociodemographic variations had almost no impact on the risk estimates. However, adjustments for indications of cancer and/or cardiovascular disease decreased the risk estimates, with ERR for total noncancer respiratory diseases declined by 35% from 0.17 to 0.11. Although it was impossible to fully adjust for the misdiagnosis of other diseases as noncancer respiratory diseases deaths in this study because of limitations of available data, nevertheless, the associations were reduced or eliminated by the adjustment that could be made. This helps demonstrates that the association between noncancer respiratory diseases and radiation exposure in previous reports could be in part be attributed to coincident cancer and/or cardiovascular diseases.

Comparison between oscillometric- and Doppler-ABI in elderly individuals.

Peripheral arterial disease (PAD) generally remains under-recognized, mainly due to the specialized technical skills required to detect the low values of the ankle-brachial index (ABI). As a simpler and faster alternative to the standard method using continuous-wave Doppler ultrasound, we evaluated automated oscillometric ABI measurement by VP-2000 with an elderly cohort of 113 subjects (age range, 61 to 88 years). The standard deviation in ABIs measured by the Doppler method was statistically greater than that measured by the oscillometric method for each of the two legs (P < 0.001). Correlations in ABIs between the two methods were 0.46 for the left leg and 0.61 for the right leg; this result appears to have been caused by interobserver variation in the Doppler ABI measurements. While the trend showing greater differences between average oscillometric- and Doppler-ABIs was significant at the lower ABI ranges, there was little indication of differences in measurements having an average ABI > 1.1. The difference between the methods was suggestively larger in subjects who were smokers than in non-smokers (P = 0.09), but the difference was not affected by other potential atherosclerotic risk factors, including age at examination (P > 0.50). A larger difference at lower ABIs led to better PAD detection by the Doppler method compared to the oscillometric method (sensitivity = 50%, specificity = 100%), although the overall agreement was not small (Cohen's Kappa = 0.65). Our findings indicate that oscillometric devices can provide more accurate estimation of the prevalence of PAD in elderly individuals than the conventional Doppler method.

A prospective follow-up study of the association of radiation exposure with fatal and non-fatal stroke among atomic bomb survivors in Hiroshima and Nagasaki (1980-2003).

OBJECTIVE: Use of medical radiotherapy has increased markedly in recent decades. Whether the consequence includes an increased risk of cardiovascular disease remains to be determined. The purpose of this study was to examine the association between radiation exposure and the incidence of stroke among Japanese atomic bomb survivors. DESIGN: A prospective follow-up study. SETTING AND PARTICIPANTS: Radiation exposure from the atomic bombing was assessed in 9515 subjects (34.8% men) with 24-year follow-up from 1980. Subjects were free of prevalent stroke when follow-up began. OUTCOME MEASURES: Stroke events and the underlying cause of death were reviewed to confirm the first-ever stroke. Subtypes (ischaemic and haemorrhagic events) were categorised based on established criteria according to the definitions of typical/atypical stroke symptoms. RESULTS: Overall mean radiation dose (±SD) in units of gray (Gy) was 0.38±0.58 (range: 0-3.5). During the study period, 235 haemorrhagic and 607 ischaemic events were identified. For men, after adjusting for age and concomitant risk factors, the risk of haemorrhagic stroke rose consistently from 11.6 to 29.1 per 10 000 person-years as doses increased from <0.05 to ≥2 Gy (p=0.009). Incidence also rose within the dose range <1 Gy (p=0.004) with no dose threshold. In women, the risk of haemorrhagic stroke rose with increasing radiation exposure but not until doses reached a threshold of 1.3 Gy (95% CI 0.5 to 2.3). Among women, for doses <1.3 Gy, differences in stroke risk were modest (13.5 per 10 000 person-years), while it increased to 20.3 per 10 000 person-years for doses that ranged from 1.3 to <2.2 Gy and to 48.6 per 10 000 person-years for doses that were higher (p=0.002). In both sexes, dose was unrelated to ischaemic stroke. CONCLUSION: While the risk of haemorrhagic stroke increases with rising radiation exposure for both sexes, effects in women are less apparent until doses exceed a threshold at 1.3 Gy.

Height loss starting in middle age predicts increased mortality in the elderly.

The purpose of this study was to determine the mortality risk among Japanese men and women with height loss starting in middle age, taking into account lifestyle and physical factors. A total of 2498 subjects (755 men and 1743 women) aged 47 to 91 years old underwent physical examinations during the period 1994 to 1995. Those individuals were followed for mortality status through 2003. Mortality risk was estimated using an age-stratified Cox proportional hazards model. In addition to sex, adjustment factors such as radiation dose, lifestyle, and physical factors measured at the baseline--including smoking status, alcohol intake, total cholesterol, blood pressure, and diagnosed diseases--were used for analysis of total mortality and mortality from each cause of death. There were a total of 302 all-cause deaths, 46 coronary heart disease and stroke deaths, 58 respiratory deaths including 45 pneumonia deaths, and 132 cancer deaths during the follow-up period. Participants were followed for 20,787 person-years after baseline. Prior history of vertebral deformity and hip fracture were not associated with mortality risk. However, more than 2 cm of height loss starting in middle age showed a significant association with all-cause mortality among the study participants (HR = 1.76, 95% CI 1.31 to 2.38, p = 0.0002), after adjustment was made for sex, attained age, atomic-bomb radiation exposure, and lifestyle and physical factors. Such height loss also was significantly associated with death due to coronary heart disease or stroke (HR = 3.35, 95% CI 1.63 to 6.86, p = 0.0010), as well as respiratory-disease death (HR = 2.52, 95% CI 1.25 to 5.22, p = 0.0130), but not cancer death. Continuous HL also was associated with all-cause mortality and CHD- or stroke-caused mortality. Association between height loss and mortality was still significant, even after excluding persons with vertebral deformity. Height loss of more than 2 cm starting in middle age was an independent risk factor for cardiovascular and respiratory-disease mortality among the elderly, even after adjusting for potential risk factors.

Lifetime risk of stroke and impact of hypertension: estimates from the adult health study in Hiroshima and Nagasaki.

Very few reports have been published on lifetime risk (LTR) of stroke by blood pressure (BP) group. This study included participants in the Radiation Effects Research Foundation Adult Health Study who have been followed up by biennial health examinations since 1958. We calculated the LTR of stroke for various BP-based groups among 7847 subjects who had not been diagnosed with stroke before the index age of 55 years using cumulative incidence analysis adjusting for competing risks. By 2003, 868 subjects had suffered stroke (512 (58.9%) were women and 542 (62.4%) experienced ischemic stroke). BP was a significant factor in determining risk of stroke for men and women, with distributions of cumulative risk for stroke significantly different across BP groups. The LTR of all-stroke for normotension (systolic BP/diastolic BP < 120/80 mm Hg), prehypertension (120-139/80-89 mm Hg), stage 1 hypertension (140-159/90-99 mm Hg) and stage 2 hypertension (> 160/100 mm Hg) were 13.8-16.9-25.8-25.8% in men and 16.0-19.9-24.0-30.5% in women, respectively (P < 0.001 among BP groups in both sexes). The estimates did not differ significantly (P = 0.16) between normotensive and prehypertensive subjects. One in five Japanese atomic bomb survivor subjects experienced stroke over their lifetime from the age of 55 years. Long-term stroke risks were elevated in those with hypertension (> 140/90 mm Hg) at any of the index ages of 45, 55, 65 and 75 years.

Risk factors for hepatocellular carcinoma in a Japanese population: a nested case-control study.

BACKGROUND: Epidemiologic studies have shown effects of lifestyle-related factors on risk for hepatocellular carcinoma. However, few cohort studies have incorporated, in a strict and in-depth manner, hepatitis B virus (HBV) and hepatitis C virus (HCV) infections or investigated synergism between such factors. METHODS: We conducted a nested case-control study using sera stored before hepatocellular carcinoma diagnosis in the longitudinal cohort of atomic bomb survivors. The study included 224 hepatocellular carcinoma cases and 644 controls that were matched to the cases on gender, age, city, time of serum storage, and method of serum storage, and countermatched on radiation dose. RESULTS: Univariate analysis showed that HBV and HCV infections, alcohol consumption, smoking habit, body mass index (BMI), and diabetes mellitus were associated with increased hepatocellular carcinoma risk, whereas coffee drinking was associated with decreased hepatocellular carcinoma risk. Multivariate relative risks of hepatocellular carcinoma (95% confidence interval) were 45.8 (15.2-138), 101 (38.7-263), 70.7 (8.3-601), 4.36 (1.48-13.0), and 4.57 (1.85-11.3), for HBV infection alone, HCV infection alone, both HBV and HCV infections, alcohol consumption of > or =40 g of ethanol per day, and BMI of >25.0 kg/m(2) 10 years before diagnosis, respectively. HBV and HCV infection and BMI of >25.0 kg/m(2) remained independent risk factors even after adjusting for severity of liver fibrosis. Among HCV-infected individuals, the relative risk of hepatocellular carcinoma for a 1 kg/m(2) increase in BMI was 1.39 (P = 0.003). CONCLUSIONS: To limit the risk for hepatocellular carcinoma, control of excess weight may be crucial for individuals with chronic liver disease, especially those with chronic hepatitis C.