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.

Serum interleukin-6 associated with hepatocellular carcinoma risk: a nested case-control study.

Inflammatory markers have been associated with increased risk of several cancers, including colon, lung, breast and liver, but the evidence is inconsistent. We conducted a nested case-control study in the longitudinal cohort of atomic-bomb survivors. The study included 224 hepatocellular carcinoma (HCC) cases and 644 controls individually matched to cases on gender, age, city and time and method of serum storage, and countermatched on radiation dose. We measured C-reactive protein (CRP) and interleukin (IL)-6 using stored sera obtained within 6 years before HCC diagnosis from 188 HCC cases and 605 controls with adequate volumes of donated blood. Analyses with adjustment for hepatitis virus infection, alcohol consumption, smoking habit, body mass index (BMI) and radiation dose showed that relative risk (RR) of HCC [95% confidence interval (CI)] in the highest tertile of CRP levels was 1.94 (0.72-5.51) compared to the lowest tertile (p = 0.20). RR of HCC (95% CI) in the highest tertile of IL-6 levels was 5.12 (1.54-20.1) compared to the lowest tertile (p = 0.007). Among subjects with BMI > 25.0 kg/m(2) , a stronger association was found between a 1-standard deviation (SD) increase in log IL-6 and HCC risk compared to subjects in the middle quintile of BMI (21.3-22.9 kg/m(2) ), resulting in adjusted RR (95% CI) of 3.09 (1.78-5.81; p = 0.015). The results indicate that higher serum levels of IL-6 are associated with increased HCC risk, independently of hepatitis virus infection, lifestyle-related factors and radiation exposure. The association is especially pronounced among subjects with obesity.

Relationship between anthropometric factors, radiation exposure, and colon cancer incidence in the Life Span Study cohort of atomic bomb survivors.

PURPOSE: We examined colon cancer risk in atomic bomb survivors to investigate whether excess body weight after the bombings alters sensitivity to radiation effects. METHODS: Of the 56,064 Japanese atomic bomb survivors with follow-up through 2002 with self-reported anthropometric data obtained from periodic mail surveys, 1,142 were diagnosed with colon cancer. We evaluated the influence of body mass index (BMI) and height on radiation-associated colon cancer risk using Poisson regression. RESULTS: We observed a similar linear dose-response relationship for the 56,064 subjects included in our analysis and the entire cohort of Japanese atomic bomb survivors [excess relative risk (ERR) per Gray (Gy) = 0.53, 95 % confidence interval (CI) 0.25-0.86]. Elevation in earliest reported BMI, BMI reported closest to colon cancer diagnosis, and time-varying BMI were associated with an elevated risk of colon cancer [relative risk (RR) per 5 kg/m(2) increase in BMI = 1.14, 95 % CI 1.03-1.26; RR = 1.16, 95 % CI 1.05-1.27; and RR = 1.15, 95 % CI 1.04-1.27, respectively]. Height was not significantly related to colon cancer risk. Inclusion of anthropometric variables in models had little impact on radiation risk estimates, and there was no evidence that sensitivity to the effect of radiation on colon cancer risk depended on BMI. CONCLUSIONS: Radiation exposure and BMI are both risk factors for colon cancer. BMI at various times after exposure to the atomic bombings does not significantly influence the relationship between radiation dose and colon cancer risk, suggesting that BMI and radiation impact colon cancer risk independently of each other.

Radiation risk of individual multifactorial diseases in offspring of the atomic-bomb survivors: a clinical health study.

There is no convincing evidence regarding radiation-induced heritable risks of adult-onset multifactorial diseases in humans, although it is important from the standpoint of protection and management of populations exposed to radiation. The objective of the present study was to examine whether parental exposure to atomic-bomb (A-bomb) radiation led to an increased risk of common polygenic, multifactorial diseases-hypertension, hypercholesterolaemia, diabetes mellitus, angina pectoris, myocardial infarction or stroke-in the first-generation (F1) offspring of A-bomb survivors. A total of 11,951 F1 offspring of survivors in Hiroshima or Nagasaki, conceived after the bombing, underwent health examinations to assess disease prevalence. We found no evidence that paternal or maternal A-bomb radiation dose, or the sum of their doses, was associated with an increased risk of any multifactorial diseases in either male or female offspring. None of the 18 radiation dose-response slopes, adjusted for other risk factors for the diseases, was statistically significantly elevated. However, the study population is still in mid-life (mean age 48.6 years), and will express much of its multifactorial disease incidence in the future, so ongoing longitudinal follow-up will provide increasingly informative risk estimates regarding hereditary genetic effects for incidence of adult-onset multifactorial disease.

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.

Incidence and prognostic value of early repolarization pattern in the 12-lead electrocardiogram.

BACKGROUND: Early repolarization pattern is a common ECG finding characterized by J-point elevation and QRS notching or slurring in the inferior and/or lateral leads, yet little is known about its incidence and long-term prognosis in Asian populations. METHODS AND RESULTS: We reviewed all the ECG records of the 5976 atomic-bomb survivors who were examined at least once during our biennial health examination in Nagasaki, Japan, between July 1958 and December 2004. We defined early repolarization pattern as ≥0.1-mV elevation of the J point or ST segment, with notching or slurring in at least 2 inferior and/or lateral leads. We assessed unexpected, cardiac, and all-cause death risk by Cox analysis. We identified 1429 early repolarization pattern cases (779 incident cases) during follow-up, yielding a positive rate of 23.9% and an incidence rate of 715 per 100 000 person-years. Early repolarization pattern had an elevated risk of unexpected death (hazard ratio, 1.83; 95% confidence interval, 1.12 to 2.97; P=0.02) and a decreased risk of cardiac (hazard ratio, 0.75; 95% confidence interval, 0.60 to 0.93; P<0.01) and all-cause (hazard ratio, 0.85; 95% confidence interval, 0.78 to 0.93; P<0.01) death. In addition, both slurring and notching were related to higher risk of unexpected death (hazard ratio, 2.09; 95% confidence interval, 1.06 to 4.12; P=0.03), as was early repolarization pattern manifestation in both inferior and lateral leads (hazard ratio, 2.50; 95% confidence interval, 1.29 to 4.83; P<0.01). CONCLUSIONS: Early repolarization pattern is associated with an elevated risk of unexpected death and a decreased risk of cardiac and all-cause death. Specific early repolarization pattern morphologies and location are associated with an adverse prognosis.

Radiation dose and cataract surgery incidence in atomic bomb survivors, 1986-2005.

PURPOSE: To examine the incidence of clinically important cataracts in relation to lens radiation doses between 0 and approximately 3 Gy to address risks at relatively low brief doses. MATERIALS AND METHODS: Informed consent was obtained, and human subjects procedures were approved by the ethical committee at the Radiation Effects Research Foundation. Cataract surgery incidence was documented for 6066 atomic bomb survivors during 1986-2005. Sixteen risk factors for cataract, such as smoking, hypertension, and corticosteroid use, were not confounders of the radiation effect on the basis of Cox regression analysis. Radiation dose-response analyses were performed for cataract surgery incidence by using Poisson regression analysis, adjusting for demographic variables and diabetes mellitus, and results were expressed as the excess relative risk (ERR) and the excess absolute risk (EAR) (ie, measures of how much radiation multiplies [ERR] or adds to [EAR] the risk in the unexposed group). RESULTS: Of 6066 atomic bomb survivors, 1028 underwent a first cataract surgery during 1986-2005. The estimated threshold dose was 0.50 Gy (95% confidence interval [CI]: 0.10 Gy, 0.95 Gy) for the ERR model and 0.45 Gy (95% CI: 0.10 Gy, 1.05 Gy) for the EAR model. A linear-quadratic test for upward curvature did not show a significant quadratic effect for either the ERR or EAR model. The linear ERR model for a 70-year-old individual, exposed at age 20 years, showed a 0.32 (95% CI: 0.09, 0.53) [corrected] excess risk at 1 Gy. The ERR was highest for those who were young at exposure. CONCLUSION: These data indicate a radiation effect for vision-impairing cataracts at doses less than 1 Gy. The evidence suggests that dose standards for protection of the eye from brief radiation exposures should be 0.5 Gy or less.

Impact of radiation and hepatitis virus infection on risk of hepatocellular carcinoma.

UNLABELLED: In cohort studies of atomic bomb survivors and Mayak nuclear facility workers, radiation-associated increases in liver cancer risk were observed, but hepatitis B virus (HBV) and hepatitis C virus (HCV) infections were not taken strictly into account. We identified 359 hepatocellular carcinoma (HCC) cases between 1970 and 2002 in the cohort of atomic bomb survivors and estimated cumulative incidence of HCC by radiation dose. To investigate contributions of radiation exposure and hepatitis virus infection to HCC risk, we conducted a nested case-control study using sera stored before HCC diagnosis in the longitudinal cohort of atomic bomb survivors. The study included 224 HCC cases and 644 controls that were matched to the cases on gender, age, city, and time and method of serum storage, and countermatched on radiation dose. The cumulative incidence of HCC by follow-up time and age increased significantly with radiation dose. The relative risk (RR) of HCC for radiation at 1 Gy was 1.67 (95% confidence interval: 1.22-2.35) with adjustment for alcohol consumption, body mass index (BMI), and smoking habit, whereas the RRs for HBV or HCV infection alone were 63 (20-241) and 83 (36-231) with such adjustment, respectively. Those estimates changed little when radiation and hepatitis virus infection were fit simultaneously. The RR of non-B, non-C HCC at 1 Gy was 1.90 (1.02-3.92) without adjustment for alcohol consumption, BMI, or smoking habit and 2.74 (1.26-7.04) with such adjustment. CONCLUSION: These results indicate that radiation exposure and HBV and HCV infection are associated independently with increased HCC risk. In particular, radiation exposure was a significant risk factor for non-B, non-C HCC with no apparent confounding by alcohol consumption, BMI, or smoking habit.

Relationship Between Radiation Exposure and Incident Atrial Fibrillation Among Atomic Bomb Survivors.

Background: Atrial fibrillation (AF) is a common arrhythmia. Although radiation exposure is associated with an elevated risk of cardiovascular disease, the effects of radiation on arrhythmia, especially AF, are unclear. We evaluated the relationship between radiation and AF in a cohort of atomic bomb survivors. Methods and Results: From a baseline enrollment period (1967-1969) to 2009, 7,379 Hiroshima and Nagasaki atomic bomb survivors (mean baseline age 50.6 years, 65.8% women, 72.9% from Hiroshima) without AF and who had been exposed to estimated radiation doses between 0 and 3.614 Gy were followed-up once every 2 years. AF was identified by 12-lead electrocardiograms and medical records. Treating age as the time scale, AF incidence was modeled with Cox proportional hazards models adjusting for demographics, AF risk factors, and radiation. We modeled radiation as both a continuous variable and categorized according to radiation dose (Control [<0.005 Gy] and 5 equal-sized groups based on radiation dose quintiles in the cohort). Over 4 decades of follow-up, we identified 276 AF cases in 176,687 person-years, for an incidence rate of 1.56 per 1,000 person-years. After adjusting for sex and city, neither categorized, linear, nor linear-quadratic models showed substantive evidence of radiation effects. Similar results were obtained after adjusting for AF risk factors. Conclusions: There were no clear positive associations between radiation dose and AF risk, rather null or non-significant inverse associations.

Metabolic cardiovascular disease risk factors and their clustering in subclinical hypothyroidism.

OBJECTIVE: A possible association between subclinical hypothyroidism and cardiovascular disease (CVD) has been reported. Monitoring of atomic-bomb survivors for late effects of radiation exposure at the Radiation Effects Research Foundation has provided the opportunity to examine associations between subclinical hypothyroidism and metabolic CVD risk factors. The objective of the study was to evaluate associations between subclinical hypothyroidism and metabolic CVD risk factors, and a cluster of these factors. DESIGN AND PARTICIPANTS: This was a cross-sectional study of 3549 subjects (mean age 70 years; 1221 men and 2328 women) between 2000 and 2003 comprising 306 subjects with subclinical hypothyroidism and 3243 control euthyroid subjects in Japan. MEASUREMENTS: We investigated associations between subclinical hypothyroidism and metabolic CVD risk factors such as hypertension, diabetes mellitus, dyslipidaemia and hyperuricaemia, and a cluster of these factors. RESULTS: Subclinical hypothyroidism was not significantly associated with either hypertension, diabetes mellitus or hyperuricaemia defined by taking into account the use of medications in both men and women, but in men it was associated with dyslipidaemia (P = 0.02). We observed a significantly increased odds ratio (OR) for the presence of three or more metabolic CVD risk factors in men with subclinical hypothyroidism after adjusting for age, body mass index (BMI), and smoking status [OR: 1.83, 95% confidence interval (CI): 1.13-2.94, P = 0.01]. The significant associations remained after an additional adjustment for atomic-bomb radiation dose. CONCLUSIONS: There appears to be a significant increase in a cluster of metabolic CVD risk factors among people with subclinical hypothyroidism.

LTA 252GG and GA genotypes are associated with diffuse-type noncardia gastric cancer risk in the Japanese population.

BACKGROUND: There are limited numbers of reports on the association of lymphotoxin-alpha (LTA) genotypes with gastric cancer. METHODS: A nested case-control study was carried out in the longitudinal cohort of atomic bomb survivors using stored sera before diagnosis (mean, 2.3 years) and blood cells. Enrolled were 287 cases with noncardia gastric cancer of diffuse and intestinal types and three controls per case selected from cohort members matched on age, gender, city, and time and type of serum storage and counter-matched on radiation dose. RESULTS: LTA 252GG and GA genotypes were associated with the prevalence of Helicobacter pylori IgG seropositivity and higher antibody titer against H. pylori cytotoxin-associated gene A (CagA) protein in controls and they were an independent risk factor for noncardia gastric cancer of diffuse type (RR = 2.8 (95% CI: 1.3-6.3), p = .01, and RR = 2.7 (95% CI: 1.5-4.8), p < .001), but not for intestinal type, after adjusting for H. pylori IgG seropositivity, CagA antibody titers, chronic atrophic gastritis, smoking, and radiation dose. Cessation of smoking (RR = 0.4 (95% CI: 0.2-0.7), p < .001) and never smoking (RR = 0.4 (95% CI: 0.3-0.6), p < .001) were both protective for future noncardia gastric cancer. Radiation dose was associated with noncardia gastric cancer in subjects with both the LTA 252G-allele and never smoking/quit smoking histories (RR = 3.8 (95% CI: 1.7-5.9), p = .009). CONCLUSION: The LTA 252 genotype is associated with noncardia gastric cancer of diffuse type in Japan and interacted with radiation dose.

Thyroid diseases in atomic bomb survivors exposed in utero.

OBJECTIVE: The objective of the study was to evaluate the association of thyroid disease with radiation dose in atomic bomb survivors exposed in utero. DESIGN: This was a cross-sectional study. SETTING: The study was conducted in atomic bomb survivors in Hiroshima and Nagasaki, Japan. PARTICIPANTS: Participants included 328 atomic bomb survivors exposed in utero (mean age 55.2 yr, 162 males) who participated in the thyroid study at the Radiation Effects Research Foundation. Examinations were conducted between March 2000 and February 2003. MAIN OUTCOME MEASURES: The relationships of various thyroid conditions to atomic bomb radiation dose were measured. RESULTS: Among the 319 participants excluding nine participants whose exposure radiation dose was not estimated, the mean maternal uterine radiation dose was 0.256 Gy. We observed no significant dose-response relationship for the prevalence of solid thyroid nodules (odds ratio at 1 Gy, 2.78; 95% confidence interval 0.50-11.80, P = 0.22), but the risk estimate was similar to the estimate for childhood exposures. The prevalence of cysts and autoimmune thyroid diseases was not associated with radiation dose (P > 0.30). We could not evaluate the dose response for malignant tumors or benign nodules due to the small number of cases. CONCLUSIONS: We did not observe a statistically significant linear dose response to radiation for thyroid nodules or autoimmune thyroid diseases 55-58 yr after participants' in utero exposure. However, the risk estimate for solid thyroid nodules was similar for those exposed in utero and those exposed in childhood. Because the study had limited statistical power to detect moderately sized effects, further studies are needed for a definitive conclusion.

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.

Cardiovascular disease risk among atomic bomb survivors exposed in utero, 1978-2003.

Given the well-documented association of in utero radiation exposure with childhood cancer and developmental impairments, the possibility of effects on adult onset diseases is an important issue. The objectives of the present study were to examine the effects of atomic bomb radiation dose on the incidence of hypertension, hypercholesterolemia and cardiovascular disease (myocardial infarction and stroke) among survivors exposed in utero and to compare their risk estimates with those of survivors exposed in childhood (<10 years old) at the time of the bombing. A total of 506 participants exposed in utero and 1,053 participants exposed in childhood were followed during 1978-2003 with biennial clinical examinations. There were no significant radiation dose effects for any diseases in the entire in utero-exposed cohort or in trimester-of-exposure subgroups, though there was a suggestion of an increased risk when fatal and nonfatal cardiovascular disease cases were combined. Positive radiation dose effects were found for hypertension and cardiovascular disease in the childhood-exposure cohort, but there were no statistically significant differences in the relative risks when we compared the two cohorts. Since the in utero cohort was under age 60 at the latest examination, continued follow-up is needed to document cardiovascular disease risk more fully.

White blood cell count, especially neutrophil count, as a predictor of hypertension in a Japanese population.

Although several studies have shown that high WBC count is a risk factor for hypertension, the relationship between WBC count and the incidence of hypertension in Japanese is poorly understood, as are the effects of WBC components on that relationship. Our objective was to verify in a Japanese population whether WBC or differential WBC count predicts hypertension incidence. A total of 9,383 initially hypertension-free subjects (3,356 men and 6,027 women), whose WBC counts were within the normal range (3,000 to < 10,000 cells/mm3), were followed from 1965 to 2004. During this 40-year follow-up, 4,606 subjects developed hypertension. After adjusting for conventional risk factors, including smoking status, we found that elevated WBC count was associated with hypertension incidence in a Cox regression model with both fixed and time-varying covariates for women. For men, elevated WBC count was a significant risk factor for hypertension only in the time-varying Cox-regression covariate. We also observed a significant association between increased neutrophil count and hypertension incidence among women. In a fully adjusted model, the relative risks of hypertension incidence, from the lowest to the highest quartiles of neutrophil count, were 1.00, 1.18, 1.28, and 1.22 in women (p for trend < 0.001). In conclusion, elevated WBC count predicted an increased incidence of hypertension in Japanese, especially among females. Moreover, neutrophils were the major WBC component contributing to the increased risk.

Low-positive antibody titer against Helicobacter pylori cytotoxin-associated gene A (CagA) may predict future gastric cancer better than simple seropositivity against H. pylori CagA or against H. pylori.

BACKGROUND: To investigate the IgG antibody titer against Helicobacter pylori CagA as a risk factor for future noncardia gastric cancer. METHODS: A nested case-control study was done in the longitudinal cohort of atomic bomb survivors using stored sera before diagnosis (mean, 2.3 years). Enrolled were 299 cancer cases and 3 controls per case selected from cohort members matched on age, gender, city, and time and type of serum storage and countermatched on radiation dose. RESULTS: H. pylori IgG seropositive with CagA IgG low titer was the strongest risk factor for noncardia gastric cancer [relative risk (RR), 3.9; 95% confidence interval (95% CI), 2.1-7.0; P < 0.001], especially for intestinal-type tumor (RR, 9.9, 95% CI, 3.5-27.4; P < 0.001), compared with other risk factors, H. pylori IgG seropositive with CagA IgG negative (RR, 2.2; 95% CI, 1.3-3.9; P = 0.0052), H. pylori IgG seropositive with CagA IgG high titer (RR, 2.0; 95% CI, 1.3-3.2; P = 0.0022), chronic atrophic gastritis (RR, 2.4; 95% CI, 1.8-3.3; P < 0.001), current smoking (RR, 2.3; 95% CI, 1.4-3.5; P < 0.001), or radiation dose (RR, 2.1; 95% CI, 1.2-3.1; P = 0.00193). Current smoking showed significantly higher risk for diffuse-type than intestinal-type tumors (P = 0.0372). Radiation risk was significant only for nonsmokers, all noncardia, and diffuse-type gastric cancers. CONCLUSIONS: A low CagA IgG titer is a useful biomarker to identify a high-risk group and it also provides a clue to understanding host-pathogen interaction.

Sex hormone and gender difference--role of testosterone on male predominance in Brugada syndrome.

INTRODUCTION: The clinical phenotype is 8 to 10 times more prevalent in males than in females in patients with Brugada syndrome. Brugada syndrome has been reported to be thinner than asymptomatic normal controls. We tested the hypothesis that higher testosterone level associated with lower visceral fat may relate to Brugada phenotype and male predominance. METHODS AND RESULTS: We measured body-mass index (BMI), body fat percentage (BF%), and several hormonal levels, including testosterone, in 48 Brugada males and compared with those in 96 age-matched control males. Brugada males had significantly higher testosterone (631 +/- 176 vs 537 +/- 158 ng/dL; P = 0.002), serum sodium, potassium, and chloride levels than those in control males by univariate analysis, and even after adjusting for age, exercise, stress, smoking, and medication of hypertension, diabetes, and hyperlipidemia, whereas there were no significant differences in other sex and thyroid hormonal levels. Brugada males had significantly lower BMI (22.1 +/- 2.9 vs 24.6 +/- 2.6 kg/m(2); P < 0.001) and BF% (19.6 +/- 4.9 vs 23.1 +/- 4.7%; P < 0.001) than control males. Testosterone level was inversely correlated with BMI and BF% in both groups, even after adjusting for the confounding variables. Conditional logistic regression models analysis showed significant positive and inverse association between Brugada syndrome and hypertestosteronemia (OR:3.11, 95% CI:1.22-7.93, P = 0.017) and BMI (OR:0.72, 95% CI:0.61-0.85, P < 0.001), respectively. CONCLUSIONS: Higher testosterone level associated with lower visceral fat may have a significant role in the Brugada phenotype and male predominance in Brugada syndrome.

Longitudinal analysis of blood pressure trends and prognosis in isolated systolic hypertension in elderly individuals.

BACKGROUND: With age, a larger proportion of elderly individuals have isolated systolic hypertension (ISH). However, because of a lack of longitudinal studies, much less is known about the incidence and prognosis of ISH in elderly individuals. The aims of this study were to document blood pressure (BP) trends in development of ISH in elderly individuals, and to investigate the incidence and prognosis for those with ISH. METHODS: Retrograde longitudinal analysis was conducted on 3284 subjects during 1958 to 1984. The presence of ISH in elderly individuals was defined as systolic BP of >or=160 and diastolic BP of or=60 years. Prognosis was subsequently investigated until 2002 and compared with that for age- and sex-matched non-ISH control subjects. RESULTS: Selected as ISH in elderly individuals were 185 subjects. Three subtypes were documented by BP trends: 71 subjects with "de novo" ISH, 68 with "burned out" ISH, and 46 subjects with "unclassifiable" ISH. Incidence of ISH increased with age. Mean onset age of ISH was 71.0 years. Subsequent follow-up revealed that the subjects with ISH lived long lives: 83.2% of ISH subjects and 76.2% of control subjects lived to be >80 years old. However, 58.9% of ISH subjects were found to have cardiovascular disease during the follow-up, showing a higher prevalence than among control subjects (42.2%, P = .0013). In more than 40% of subjects with ISH, cardiovascular disease occurred at >or=80 years of age. CONCLUSIONS: In this study, the incidence of ISH increased with age. Persons with ISH have good prognoses in terms of longevity, but many have late-onset cardiovascular complications, suggesting the importance of BP control even in very elderly individuals.

Systolic blood pressure and systolic hypertension in adolescence of atomic bomb survivors exposed in utero.

Annual medical examinations were conducted during adolescence for the in utero clinical study sample subjects exposed prenatally to the atomic bombs in Hiroshima and Nagasaki. Systolic blood pressure and several anthropometric measurements were recorded during these examinations. For 1014 persons exposed in utero, two types of longitudinal analyses were performed, for a total of 7029 observations (6.93 observations per subject) of systolic blood pressure (continuous data) and systolic hypertension (binary data) for persons aged 9 to 19 years. Body mass index (BMI) and/or body weight were considered in the analyses as potential confounders. For the measurements of systolic blood pressure, the common dose effect was 2.09 mmHg per Gy and was significant (P = 0.017). The dose by trimester interaction was suggestive (P = 0.060). A significant radiation dose effect was found in the second trimester (P = 0.001), with an estimated 4.17 mmHg per Gy, but in the first and third trimesters, radiation dose effects were not significant (P > 0.50). For prevalence of systolic hypertension, the radiation dose effect was significant (P = 0.009); the odds ratio at 1 Gy was 2.23 [95% confidence interval (CI): 1.23, 4.04], and the dose by trimester interaction was not significant (P = 0.778). The dose response of systolic hypertension had no dose threshold, with a threshold point estimate of 0 Gy (95% CI: <0.0, 1.1 Gy). The dose response for systolic blood pressure was most pronounced in the second trimester, the most active organogenesis period for the organs relevant to blood pressure.

Postoperative cataract cases among atomic bomb survivors: radiation dose response and threshold.

Recent evidence argues against a high threshold dose for vision-impairing radiation-induced cataractogenesis. We conducted logistic regression analysis to estimate the dose response and used a likelihood profile procedure to determine the best-fitting threshold model among 3761 A-bomb survivors who underwent medical examinations during 2000-2002 for whom radiation dose estimates were available, including 479 postoperative cataract cases. The analyses indicated a statistically significant dose-response increase in the prevalence of postoperative cataracts [odds ratio (OR), 1.39; 95% confidence interval (CI), 1.24-1.55] at 1 Gy, with no indication of upward curvature in the dose response. The dose response was suggestive when the restricted dose range of 0 to 1 Gy was examined. A nonsignificant dose threshold of 0.1 Gy (95% CI, <0-0.8) was found. The prevalence of postoperative cataracts in A-bomb survivors increased significantly with A-bomb radiation dose. The estimate (0.1 Gy) and upper bound (0.8 Gy) of the dose threshold for operative cataract prevalence was much lower than the threshold of 2-5 Gy usually assumed by the radiation protection community and was statistically compatible with no threshold at all.