Impact of new antiretroviral combination therapies in HIV infected patients in Switzerland: prospective multicentre study. Swiss HIV Cohort Study.

OBJECTIVES: To examine trends in disease progression and survival among patients enrolled in the Swiss HIV cohort study during 1988-96 and to assess the influence of new antiretroviral combination therapies. DESIGN: Prospective multicentre study, with follow up visits planned at six monthly intervals. SETTING: Seven HIV units at university centres and cantonal hospitals in Switzerland. PATIENTS: 3785 men (mean age 35.0 years) and 1391 women (30.3 years) infected with HIV. 2023 participants had a history of intravenous drug misuse; 1764 were men who had sex with men; 1261 were infected heterosexually; and 164 had other or unknown modes of transmission. 601 participants had had an AIDS defining illness. RESULTS: During more than 15,000 years of follow up, there were 1456 first AIDS defining diagnoses and 1903 deaths. Compared with those enrolled during 1988-90, the risk of progression to a first AIDS diagnosis was reduced by 18% (relative risk 0.82 (95% confidence interval 0.73 to 0.93)) among participants enrolled in 1991-2, by 23% (0.77 (0.65 to 0.91)) among those enrolled in 1993-4, and by 73% (0.27 (0.18 to 0.39)) among those enrolled in 1995-6. Mortality was reduced by 19% (0.81 (0.73 to 0.90)), 26% (0.74 (0.63 to 0.87)), and 62% (0.38 (0.25 to 0.97)) respectively. Compared with no antiretroviral treatment, the risk of an initial AIDS diagnosis after CD4 lymphocyte counts fell to < 200 cells x 10(6)/1 was reduced by 16% (0.84 (0.73 to 0.97)) with monotherapy, 24% (0.76 (0.63 to 0.91)) with dual therapy, and 42% (0.58 (0.37 to 0.92)) with triple therapy. Mortality was reduced by 23% (0.77 (0.68 to 0.88)), 31% (0.69 (0.60 to 0.80)), and 65% (0.35 (0.20 to 0.60)) respectively. CONCLUSIONS: The introduction of antiretroviral combination therapies outside the selected patient groups included in clinical trials has led to comparable reductions in disease progression and mortality.     

Increased morbidity and mortality related to asthma among asthmatic patients who use major tranquillisers.

OBJECTIVE--To assess the potentially increased risk of death or near death from asthma in asthmatic patients with psychosis. DESIGN--Case-control study. SETTING--The computerised health databases of the Canadian province of Saskatchewan. SUBJECTS--131 cases of death or near death from asthma identified within a cohort of asthmatic patients; 3930 matched non-cases. EXPOSURE AND OUTCOME MEASURES--The exposure of interest was the use of major tranquillisers in the period before an outcome event. Outcomes included death or near death from asthma. RESULTS--Crude analyses showed that asthmatic patients who had used major tranquillisers in the previous 12 months were at a 3.2 (95% confidence interval 1.4 to 7.5) times greater risk of death or near death from asthma than asthmatic patients who did not use major tranquillisers. Past users of major tranquillisers who had recently discontinued use were at a particularly high risk (relative risk 6.6; 2.5 to 17.6). Adjustment for use of antiasthma drugs and other confounders abolished this excess risk. CONCLUSIONS--Asthmatic patients who use major tranquillisers seem to be at an increased risk of death or near death from asthma. Physicians treating asthmatic patients with a history of use of major tranquillisers should exercise greater caution with regard to management of such patients.     

Serevent nationwide surveillance study: comparison of salmeterol with salbutamol in asthmatic patients who require regular bronchodilator treatment.

OBJECTIVE--To compare safety of salmeterol and salbutamol in treating asthma. DESIGN--Double blind, randomised clinical trial in parallel groups over 16 weeks. SETTING--General practices throughout the United Kingdom. SUBJECTS--25,180 patients with asthma considered to require regular treatment with bronchodilators who were recruited by their general practitioner (n = 3516). INTERVENTIONS--Salmeterol (Serevent) (50 micrograms twice daily) or salbutamol (200 micrograms four times a day) randomised in the ratio of two patients taking salmeterol to one taking salbutamol. All other drugs including prophylaxis against asthma were continued throughout the study. MAIN OUTCOME MEASURES--All serious events and reasons for withdrawals (medical and non-medical) whether or not they were considered to be related to the drugs. RESULTS--Fewer medical withdrawals due to asthma occurred in patients taking salmeterol than in those taking salbutamol (2.91% v 3.79%; chi 2 = 13.6, p = 0.0002). Mortality and admissions to hospital were as expected. There was a small but non-significant excess mortality in the group taking salmeterol and a significant excess of asthma events including deaths in patients with severe asthma on entry. Use of more than two canisters of bronchodilator a month was particularly associated with the occurrence of an adverse asthma event. CONCLUSIONS--Treatment over 16 weeks with either salmeterol or salbutamol was not associated with an incidence of deaths related to asthma in excess of that predicted. Overall control of asthma was better in patients allocated to salmeterol. Serious adverse events occurred in patients most at risk on entry and were probably due to the disease rather than treatment.     

Mortality in over 350,000 Insured Swedish dogs from 1995–2000: I. Breed-, Gender-, Age- and Cause-specific Rates

This study presents data on over 350,000 insured Swedish dogs up to 10 years of age contributing to over one million dog-years at risk (DYAR) during 1995–2000. A total of 43,172 dogs died or were euthanised and of these 72% had a claim with a diagnosis for the cause of death. The overall total mortality was 393 deaths per 10,000 DYAR. Mortality rates are calculated for the 10 most common breeds, 10 breeds with high mortality and a group including all other breeds, crudely and for general causes of death. Proportional mortality is presented for several classifications. Five general causes accounted for 62% of the deaths with a diagnosis (i.e. tumour (18%), trauma (17%), locomotor (13%), heart (8%) and neurological (6%)). Mortality rates for the five most common diagnoses within the general causes of death are presented. These detailed statistics on mortality can be used in breed-specific strategies as well as for general health promotion programs. Further details on survival and relative risk by breed and age are presented in the companion paper [14].     

What are the complications of influenza and can they be prevented? Experience from the 1989 epidemic of H3N2 influenza A in general practice.

OBJECTIVES--In an epidemic: to measure the incidence and risk of complications of influenza; to determine the effect of pre-existing disease on complications; to estimate vaccine uptake and efficacy. DESIGN--Case-control study. SETTING--Primary care: two group practices. SUBJECTS--342 of the 395 cases of clinically diagnosed influenza reported to the general practice surveillance of infectious diseases scheme of the Public Health Laboratory Service during the 1989 epidemic, and 342 age and sex matched controls. INTERVENTIONS--Examination of records. MAIN OUTCOME MEASURES--Documented recognised complications; hospital admission; previous vaccination. RESULTS--Of 15 recognised complications, bronchitis was the commonest (rate 190.1/1000 cases) and significantly commoner in cases (summary odds ratio 9.7) after adjusting for higher consultation rates (mean 6.1 per annum v 4.2 among controls; p < 0.0001). No deaths were recorded. The risk of bronchitis complicating influenza was higher in patients with pre-existing illnesses regarded as an indication for vaccination (odds ratio 3.3; p < 0.0001). Observed vaccination efficacy in those with pre-existing illnesses and in elderly subjects was high (63% and 77% respectively) but uptake was low (4.5% and 6.1% respectively). CONCLUSIONS--Bronchitis complicates about one fifth of all cases of influenza presenting to general practitioners. Patients with pre-existing illnesses regarded as an indication for vaccination are particularly at risk. Vaccine uptake is extremely low, precluding an unequivocal demonstration of a protective effect.     

Threat of unemployment and cardiovascular risk factors: longitudinal study of quality of sleep and serum cholesterol concentrations in men threatened with redundancy.

OBJECTIVE--To assess whether the threat of unemployment affects risk factors for cardiovascular disease. DESIGN--Longitudinal study of a cohort of middle aged shipyard workers followed up for a mean of 6.2 (SD 1.9) years and a group of controls observed for the same period. The first investigation took place during a period of relative economic stability for the shipyard and the second during the phase of its closure. SETTING--An age cohort health screening programme in Malmö, Sweden. PARTICIPANTS--715 Male shipyard workers and 261 age matched male controls. MAIN OUTCOME MEASURES--Changes in 19 variables related to the risk of cardiovascular disease, and psychological variables, alcohol consumption, smoking, and dietary habits as assessed by questionnaire. RESULTS--Serum cholesterol concentrations increased more (mean 0.25 (SD 0.68) mmol/l v 0.08 (0.66) mmol/l) and serum calcium concentrations decreased less (-0.06 (0.10) mmol/l v -0.08 (0.09) mmol/l) in the shipyard workers than in the controls. A correlation was found between scores for sleep disturbance and changes in serum cholesterol concentration. In the whole series there was a greater increase in serum cholesterol concentrations among men threatened with unemployment (437/976; 44.8%) than among those who were not. In stepwise regression analysis the change in serum cholesterol concentration was correlated with changes in haemoglobin concentration, body weight, and serum triglyceride and calcium concentrations. A positive correlation was found between change in cholesterol concentration and change in blood pressure, indicating that the overall risk profile had worsened among men with increased serum cholesterol concentrations. CONCLUSIONS--Risk of unemployment increases the serum cholesterol concentration in middle aged men, the increase being more pronounced in those with sleep disturbance. The increase in serum cholesterol is related to changes in other established risk factors for cardiovascular disease. These findings might partly explain the excessive mortality due to cardiovascular disease recorded among the unemployed and people with sleep disturbance.     

Analysis of the mortality experience amongst U.S. nuclear power industry workers after chronic low-dose exposure to ionizing radiation

Workers employed in 15 utilities that generate nuclear power in the United States have been followed for up to 18 years between 1979 and 1997. Their cumulative dose from whole body ionizing radiation has been determined from the dose records maintained by the facilities themselves and the REIRS and REMS systems maintained by the Nuclear Regulatory Commission and the Department of Energy, respectively. Mortality in the cohort from a number of causes has been analyzed with respect to individual radiation doses. The cohort displays a very substantial healthy worker effect, i.e. considerably lower cancer and noncancer mortality than the general population. Based on 26 and 368 deaths, respectively, positive though statistically nonsignificant associations were seen for mortality from leukemia (excluding chronic lymphocytic leukemia) and all solid cancers combined, with excess relative risks per sievert of 5.67 [95% confidence interval (CI) -2.56, 30.4] and 0.506 (95% CI -2.01, 4.64), respectively. These estimates are very similar to those from the atomic bomb survivors study, though the wide confidence intervals are also consistent with lower or higher risk estimates. A strong positive and statistically significant association between radiation dose and deaths from arteriosclerotic heart disease including coronary heart disease was also observed in the cohort, with an ERR of 8.78 (95% CI 2.10, 20.0). While associations with heart disease have been reported in some other occupational studies, the magnitude of the present association is not consistent with them and therefore needs cautious interpretation and merits further attention. At present, the relatively small number of deaths and the young age of the cohort (mean age at end of follow-up is 45 years) limit the power of the study, but further follow-up and the inclusion of the present data in an ongoing IARC combined analysis of nuclear workers from 15 countries will have greater power for testing the main hypotheses of interest.     

Possible selection effects for radiation risk estimates in Japanese A-bomb survivors: reanalysis of acute radiation symptoms data

An earlier analysis examined the possibility of bias in the Life Span Study (LSS) cohort by studying Japanese A-bomb survivors with bomb-related acute injuries and those without such injuries (Stewart and Kneale in Int J Epidemiol 29:708–714, 2000). The authors reported significantly higher radiation risks, both for cancers and non-cancers, among those survivors with acute injuries compared with those without. The risks were reported to be particularly large among survivors aged <10 or ≥55 years of age at the time of bombings. The aim of this paper is to examine these findings more closely using the LSS acute effects data. All the analyses were carried out using Poisson regression. Relative risk models were fitted with adjustment for sex and other factors. Significant differences in relative risk between survivors with epilation and burns and those without epilation and burns are found for leukaemia. There is also some evidence for heterogeneity in the leukaemia risk between survivors with two or more acute injuries and those with no injuries, but the evidence is disappeared when survivors with one or more injuries are compared with those without injuries. For solid cancers, cardiovascular disease and all deaths combined, the risks do not differ to a statistically significant extent between survivors with and without injuries. There is no statistically significant heterogeneity in risk across age-at-exposure categories for survivors with injuries. For all deaths combined, relative risk estimates and their uncertainties are significantly higher for survivors exposed at ages <10 years when compared with other exposure ages, but risks are not significantly raised for survivors exposed at ≥55 years of age. With the exception of leukaemia, the findings from the present work are inconsistent with those of Stewart and Kneale.     

Dietary habits and mortality in 11,000 vegetarians and health conscious people: results of a 17 year follow up.

OBJECTIVE: To investigate the association of dietary habits with mortality in a cohort of vegetarians and other health conscious people. DESIGN: Observational study. SETTING: United Kingdom. SUBJECTS: 4336 men and 6435 women recruited through health food shops, vegetarian societies, and magazines. MAIN OUTCOME MEASURES: Mortality ratios for vegetarianism and for daily versus less than daily consumption of wholemeal bread, bran cereals, nuts or dried fruit, fresh fruit, and raw salad in relation to all cause mortality and mortality from ischaemic heart disease, cerebrovascular disease, all malignant neoplasms, lung cancer, colorectal cancer, and breast cancer. RESULTS: 2064 (19%) subjects smoked, 4627 (43%) were vegetarian, 6699 (62%) ate wholemeal bread daily, 2948 (27%) ate bran cereals daily, 4091 (38%) ate nuts or dried fruit daily, 8304 (77%) ate fresh fruit daily, and 4105 (38%) ate raw salad daily. After a mean of 16.8 years follow up there were 1343 deaths before age 80. Overall the cohort had a mortality about half that of the general population. Within the cohort, daily consumption of fresh fruit was associated with significantly reduced mortality from ischaemic heart disease (rate ratio adjusted for smoking 0.76 (95% confidence interval 0.60 to 0.97)), cerebrovascular disease (0.68 (0.47 to 0.98)), and for all causes combined (0.79 (0.70 to 0.90)). CONCLUSIONS: In this cohort of health conscious individuals, daily consumption of fresh fruit is associated with a reduced mortality from ischaemic heart disease, cerebrovascular disease, and all causes combined.     

Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials.

OBJECTIVE--To determine the effects of lowering cholesterol concentrations on total and cause specific mortality in randomised primary prevention trials. DESIGN--Qualitative (meta-analytic) evaluation of total mortality from coronary heart disease, cancer, and causes not related to illness in six primary prevention trials of cholesterol reduction (mean duration of treatment 4.8 years). PATIENTS--24,847 Male participants; mean age 47.5 years. MAIN OUTCOME MEASURES--Total and cause specific mortalities. RESULTS--Follow up periods totalled 119,000 person years, during which 1147 deaths occurred. Mortality from coronary heart disease tended to be lower in men receiving interventions to reduce cholesterol concentrations compared with mortality in control subjects (p = 0.06), although total mortality was not affected by treatment. No consistent relation was found between reduction of cholesterol concentrations and mortality from cancer, but there was a significant increase in deaths not related to illness (deaths from accidents, suicide, or violence) in groups receiving treatment to lower cholesterol concentrations relative to controls (p = 0.004). When drug trials were analysed separately the treatment was found to reduce mortality from coronary heart disease significantly (p = 0.04). CONCLUSIONS--The association between reduction of cholesterol concentrations and deaths not related to illness warrants further investigation. Additionally, the failure of cholesterol lowering to affect overall survival justifies a more cautious appraisal of the probable benefits of reducing cholesterol concentrations in the general population.     

The Risk of Asthma in Patients with Ankylosing Spondylitis: A Population-Based Cohort Study

BackgroundThe relationship between asthma and ankylosing spondylitis (AS) is controversial. We examined the risk of asthma among AS patients in a nationwide population.MethodsWe conducted a retrospective cohort study using data from the National Health Insurance (NHI) system of Taiwan. The cohort included 5,974 patients newly diagnosed with AS from 2000 to 2010. The date of diagnosis was defined as the index date. A 4-fold of general population without AS was randomly selected frequency matched by age, gender and the index year. The occurrence and hazard ratio (HR) of asthma were estimated by the end of 2011.ResultsThe overall incidence of asthma was 1.74 folds greater in the AS cohort than in the non-AS cohort (8.26 versus 4.74 per 1000 person-years) with a multivariable Cox method measured adjusted HR of 1.54 (95% confidence interval (CI), 1.34–1.76). The adjusted HR of asthma associated with AS was higher in women (1.59; 95% CI, 1.33–1.90), those aged 50–64 years (1.66; 95% CI, 1.31–2.09), or those without comorbidities (1.82; 95% CI, 1.54–2.13).ConclusionPatients with AS are at a higher risk of developing asthma than the general population, regardless of gender and age. The pathophysiology needs further investigation.     

Chronic low-dose exposure in the Techa River Cohort: risk of mortality from circulatory diseases

The aim of the present study was to analyze the mortality from circulatory diseases for about 30,000 members of the Techa River cohort over the period 1950–2003, and to investigate how these rates depend on radiation doses. This population received both external and internal exposures from ⁹⁰Sr, ⁸⁹Sr, ¹³⁷Cs, and other uranium fission products as a result of waterborne releases from the Mayak nuclear facility in the Southern Urals region of the Russian Federation. The analysis included individualized estimates of the total (external plus internal) absorbed dose in muscle calculated based on the Techa River Dosimetry System 2009. The cohort-average dose to muscle tissue was 35 mGy, and the maximum dose was 510 mGy. Between 1950 and 2003, 7,595 deaths from circulatory diseases were registered among cohort members with 901,563 person years at risk. Mortality rates in the cohort were analyzed using a simple parametric excess relative risk (ERR) model. For all circulatory diseases, the estimated excess relative risk per 100 mGy with a 15-year lag period was 3.6 % with a 95 % confidence interval of 0.2–7.5 %, and for ischemic heart disease it was 5.6 % with a 95 % confidence interval of 0.1–11.9 %. A linear ERR model provided the best fit. Analyses with a lag period shorter than 15 years from the beginning of exposure did not reveal any significant risk of mortality from either all circulatory diseases or ischemic heart disease. There was no evidence of an increased mortality risk from cerebrovascular disease (p > 0.5). These results should be regarded as preliminary, since they will be updated after adjustment for smoking and alcohol consumption.     

Mortality in achondroplasia.

Standardized mortality ratios (SMRs) were determined for a historical cohort of achondroplastic individuals identified through the Medical Genetics Clinics of the University of Texas Health Science Center at Houston and Johns Hopkins Hospital, Baltimore. Mortality was increased at all ages, with an overall SMR of 2.27 (95% confidence interval 1.7-3.0). Sudden death accounted for the excess deaths in those less than 4 years of age, and brain-stem compression was identified as the cause in half of these deaths. Central nervous system and respiratory causes were not significantly increased but accounted for half of the deaths in those 5-24 years of age. SMRs were not significantly increased for those greater than 34 years of age. However, deaths attributed to cardiovascular causes were increased in the 25-54-year-old age group, accounting for 10 of 17 deaths. The overall cardiovascular SMR was 5.2 (95% confidence interval 2.5-9.6). Within this group, severe disability resulting from marked spinal canal stenosis was present in a majority of individuals and may have been a contributing factor in these deaths. This study suggests that the bony abnormalities associated with achondroplasia--i.e., foramen magnum and spinal canal stenosis--may have a significant effect on mortality at all ages but particularly in children. Efforts to minimize these complications are recommended.     

Cancer mortality in a population-based cohort of American Indians – The strong heart study

BackgroundCancer mortality among American Indian (AI) people varies widely, but factors associated with cancer mortality are infrequently assessed.MethodsCancer deaths were identified from death certificate data for 3516 participants of the Strong Heart Study, a population-based cohort study of AI adults ages 45–74 years in Arizona, Oklahoma, and North and South Dakota. Cancer mortality was calculated by age, sex and region. Cox proportional hazards model was used to assess independent associations between baseline factors in 1989 and cancer death by 2010.ResultsAfter a median follow-up of 15.3 years, the cancer death rate per 1000 person-years was 6.33 (95 % CI 5.67–7.04). Cancer mortality was highest among men in North/South Dakota (8.18; 95 % CI 6.46–10.23) and lowest among women in Arizona (4.57; 95 % CI 2.87–6.92). Factors independently associated with increased cancer mortality included age, current or former smoking, waist circumference, albuminuria, urinary cadmium, and prior cancer history. Factors associated with decreased cancer mortality included Oklahoma compared to Dakota residence, higher body mass index and total cholesterol. Sex was not associated with cancer mortality. Lung cancer was the leading cause of cancer mortality overall (1.56/1000 person-years), but no lung cancer deaths occurred among Arizona participants. Mortality from unspecified cancer was relatively high (0.48/100 person-years; 95 % CI 0.32−0.71).ConclusionsRegional variation in AI cancer mortality persisted despite adjustment for individual risk factors. Mortality from unspecified cancer was high. Better understanding of regional differences in cancer mortality, and better classification of cancer deaths, will help healthcare programs address cancer in AI communities.     

Risk of death from cancer and ischaemic heart disease in meat and non-meat eaters.

OBJECTIVE--To investigate the health consequences of a vegetarian diet by examining the 12 year mortality of non-meat eaters and meat eating controls. DESIGN--Prospective observational study in which members of the non-meat eating cohort were asked to nominate friends or relatives as controls. SETTING--United Kingdom. SUBJECTS--6115 non-meat eaters identified through the Vegetarian Society of the United Kingdom and the news media (mean (SD) age 38.7 (16.8) years) and 5015 controls who were meat eaters (39.3 (15.4) years). MAIN OUTCOME MEASURES--Standardised mortality ratios for cancer, ischaemic heart disease, and total mortality in the two cohorts and death rate ratio in the non-meat eaters compared with meat eaters after adjustment for potentially confounding variables. RESULTS--Standardised mortality ratios (taking the value among the general population as 100) for ischaemic heart disease were 51 (95% confidence interval 38 to 66) for meat eaters and 28 (20 to 38) for non-meat eaters (P < 0.01). Values for all cancers were 80 (64 to 98) and 50 (39 to 62) for meat eaters and non-meat eaters respectively. After adjustment for the effects of smoking, body mass index, and socioeconomic status death rate ratios in non-meat eaters compared with meat eaters were 0.72 (0.47 to 1.10) for ischaemic heart disease and 0.61 (0.44 to 0.84) for all cancers. CONCLUSIONS--The reduced mortality from cancer among those not eating meat is not explained by lifestyle related risk factors, which have a low prevalence among vegetarians. No firm conclusion can be made about deaths from ischaemic heart disease. These data do not justify advice to exclude meat from the diet since there are several attributes of a vegetarian diet apart from not eating meat which might reduce the risk.     

Studies of the mortality of atomic bomb survivors, Report 14, 1950-2003: an overview of cancer and noncancer diseases

This is the 14th report in a series of periodic general reports on mortality in the Life Span Study (LSS) cohort of atomic bomb survivors followed by the Radiation Effects Research Foundation to investigate the late health effects of the radiation from the atomic bombs. During the period 1950-2003, 58% of the 86,611 LSS cohort members with DS02 dose estimates have died. The 6 years of additional follow-up since the previous report provide substantially more information at longer periods after radiation exposure (17% more cancer deaths), especially among those under age 10 at exposure (58% more deaths). Poisson regression methods were used to investigate the magnitude of the radiation-associated risks, the shape of the dose response, and effect modification by gender, age at exposure, and attained age. The risk of all causes of death was positively associated with radiation dose. Importantly, for solid cancers the additive radiation risk (i.e., excess cancer cases per 10(4) person-years per Gy) continues to increase throughout life with a linear dose-response relationship. The sex-averaged excess relative risk per Gy was 0.42 [95% confidence interval (CI): 0.32, 0.53] for all solid cancer at age 70 years after exposure at age 30 based on a linear model. The risk increased by about 29% per decade decrease in age at exposure (95% CI: 17%, 41%). The estimated lowest dose range with a significant ERR for all solid cancer was 0 to 0.20 Gy, and a formal dose-threshold analysis indicated no threshold; i.e., zero dose was the best estimate of the threshold. The risk of cancer mortality increased significantly for most major sites, including stomach, lung, liver, colon, breast, gallbladder, esophagus, bladder and ovary, whereas rectum, pancreas, uterus, prostate and kidney parenchyma did not have significantly increased risks. An increased risk of non-neoplastic diseases including the circulatory, respiratory and digestive systems was observed, but whether these are causal relationships requires further investigation. There was no evidence of a radiation effect for infectious or external causes of death.     

Risk of early death in extremely overweight young men.

The effect of pronounced obesity in youth on later mortality was studied in 1239 men with extreme overweight, defined as a weight/height 2 greater than or equal to 31 kg/m2, in the population of 331 919 men liable for military service in the Copenhagen area during the period 1943-1977. A random sample of 2948 drawn from the remaining study population served as a control group. All men were followed up until November 1980, by which time 33 deaths had occurred among the extremely overweight subjects compared with 89 in the control group. This gave a mortality ratio (observed to expected number of deaths) of 1.14 (95% confidence limit 0.91-1.40) for controls with a significantly greater mortality of 1.73 (95% confidence limit 1.20-2.41) for obese subjects. The relative risk, estimated from the survival time distributions, was fairly constant around 1.6 throughout the 37 years of observation. Taking into account age at and year of entry in a regression analysis did not change the relative mortality risk. The proportion of natural death was significantly higher in the obese group than in the control group until the age of 30 but not thereafter. Pronounced obesity in youth is a health hazard, manifesting itself particularly in a distinct increase in mortality from natural causes in early adulthood.     

Coronary heart disease mortality and radon exposure in the Newfoundland fluorspar miners’ cohort, 1950–2001

Kreuzer and coworkers recently reported no association between cumulative exposure to radiation and death from cardiovascular disease in a cohort of German uranium miners. Here, we report on the relationship between cumulative exposure to radon progeny and coronary heart disease among Newfoundland fluorspar miners. Previous analyses in this cohort found elevated death rates from coronary heart disease among those with higher cumulative radon exposure. However, this finding was based on a relatively small number of deaths and was not statistically significant. Since then, the follow-up of this cohort has been extended by 10 years until the end of 2001. Among the 2,070 miners in our study, 267 died from coronary heart disease. There was no trend evident between cumulative exposure to radon and the relative risk of death from coronary heart disease (P = 0.63). This finding was unchanged after adjusting for the lifetime smoking status that was available for approximately 54% of the cohort. Similarly, the cumulative radon exposure was found to be unrelated to deaths of the circulatory system, acute myocardial infarction, and cerebrovascular disease. These findings are consistent with those recently reported by Kreuzer and colleagues. We share their view that uncontrolled confounding for other coronary heart disease risk factors hinders the interpretation of the risk estimates.     

Impact of treating hyperlipidemia or hypertension to reduce the risk of death from coronary artery disease

OBJECTIVE: To compare the prevalence of modifiable risk factors for cardiovascular disease among hypertensive and nonhypertensive adults and to estimate the effect of treating hyperlipidemia or hypertension to reduce the risk of death from coronary artery disease. METHODS: The authors evaluated a sample of 7814 subjects aged 35-74 years free of clinical cardiovascular disease from the Canadian Heart Health Surveys to estimate the prevalence of cardiovascular risk factors. They identified hyperlipidemic subjects (ratio of total cholesterol to high-density lipoprotein cholesterol [total-C/HDL-C] 6.0 [corrected] or more for men and 5.0 [corrected] or more for women) and hypertensive subjects (systolic or diastolic blood pressure 160/90 mm Hg or greater, or receiving pharmacologic or nonpharmacologic treatment). A life expectancy model was used to estimate the rate of death from coronary artery disease following specific treatments. RESULTS: An elevated total-C/HDL-C ratio was significantly more common among hypertensive than nonhypertensive men aged 35-64 (rate ratio [RR] 1.56 for age 35-54, 1.28 for age 55-64) and among hypertensive than nonhypertensive women of all ages (RR 2.73 for age 35-54, 1.58 for age 55-64, 1.31 for age 65-74). Obesity and a sedentary lifestyle were also more common among hypertensive than among nonhypertensive subjects. According to the model, more deaths from coronary artery disease could be prevented among subjects with treated but uncontrolled hypertension by modifying lipids rather than by further reducing blood pressure for men aged 35-54 (reduction of 50 v. 29 deaths per 100,000) and 55-64 (reduction of 171 v. 104 deaths per 100,000) and for women aged 35-54 (reduction of 44 v. 39 deaths per 100,000). Starting antihypertensive therapy in subjects aged 35-74 with untreated hypertension would achieve a greater net reduction in deaths from coronary artery disease than would lipid lowering. Nonetheless, the benefits of lipid therapy were substantial: lipid intervention among hypertensive subjects aged 35-74 represented 36% of the total benefits of treating hyperlipidemia in the total hyperlipidemic population. INTERPRETATION: The clustering of hyperlipidemia and the potential benefits of treatment among hypertensive adults demonstrate the need for screening and treating other cardiovascular risk factors beyond simply controlling blood pressure.     

Studies of mortality of atomic bomb survivors. Report 13: Solid cancer and noncancer disease mortality: 1950-1997

This continues the series of general reports on mortality in the cohort of atomic bomb survivors followed up by the Radiation Effects Research Foundation. This cohort includes 86,572 people with individual dose estimates, 60% of whom have doses of at least 5 mSv. We consider mortality for solid cancer and for noncancer diseases with 7 additional years of follow-up. There have been 9,335 deaths from solid cancer and 31,881 deaths from noncancer diseases during the 47-year follow-up. Of these, 19% of the solid cancer and 15% of the noncancer deaths occurred during the latest 7 years. We estimate that about 440 (5%) of the solid cancer deaths and 250 (0.8%) of the noncancer deaths were associated with the radiation exposure. The excess solid cancer risks appear to be linear in dose even for doses in the 0 to 150-mSv range. While excess rates for radiation-related cancers increase throughout the study period, a new finding is that relative risks decline with increasing attained age, as well as being highest for those exposed as children as noted previously. A useful representative value is that for those exposed at age 30 the solid cancer risk is elevated by 47% per sievert at age 70. There is no significant city difference in either the relative or absolute excess solid cancer risk. Site-specific analyses highlight the difficulties, and need for caution, in distinguishing between site-specific relative risks. These analyses also provide insight into the difficulties in interpretation and generalization of LSS estimates of age-at-exposure effects. The evidence for radiation effects on noncancer mortality remains strong, with risks elevated by about 14% per sievert during the last 30 years of follow-up. Statistically significant increases are seen for heart disease, stroke, digestive diseases, and respiratory diseases. The noncancer data are consistent with some non-linearity in the dose response owing to the substantial uncertainties in the data. There is no direct evidence of radiation effects for doses less than about 0.5 Sv. While there are no statistically significant variations in noncancer relative risks with age, age at exposure, or sex, the estimated effects are comparable to those seen for cancer. Lifetime risk summaries are used to examine uncertainties of the LSS noncancer disease findings.