Occupational particle exposure and chronic kidney disease: a cohort study in Swedish construction workers.

OBJECTIVES: Increasing epidemiological and experimental evidence suggests that particle exposure is an environmental risk factor for chronic kidney disease (CKD). However, only a few case-control studies have investigated this association in an occupational setting. Hence, our objective was to investigate associations between particle exposure and CKD in a large cohort of Swedish construction workers. METHODS: We performed a retrospective cohort study in the Swedish Construction Workers' Cohort, recruited 1971-1993 (n=286 089). A job-exposure matrix was used to identify workers exposed to nine different particulate exposures, which were combined into three main categories (inorganic dust and fumes, wood dust and fibres). Incident CKD and start of renal replacement therapy (RRT) were obtained from validated national registries until 2021 and analysed using adjusted Cox proportional hazards models. RESULTS: Exposure to inorganic dust and fumes was associated with an increased risk of CKD and RRT during working age (adjusted HR for CKD at age <65 years 1.15, 95% CI 1.05 to 1.26). The elevated risk did not persist after retirement age. Exposure to cement dust, concrete dust and diesel exhaust was associated with CKD. Elevated HRs were also found for quartz dust and welding fumes. CONCLUSIONS: Workers exposed to inorganic particles seem to be at elevated risk of CKD and RRT. Our results are in line with previous evidence of renal effects of ambient air pollution and warrant further efforts to reduce occupational and ambient particle exposure.

Blood cadmium is associated with increased fracture risk in never-smokers - results from a case-control study using data from the Malmö Diet and Cancer cohort.

BACKGROUND: Several studies have shown associations between cadmium (Cd) exposure and an increased risk of fractures. However, the size of the risk is still unclear and proper adjustment for smoking is a challenge. The aim of this study was to quantify the association between dietary cadmium measured in blood and fracture risk in the general Swedish population through a large population-based case-control study in never-smokers. METHODS: The study included 2113 incident cases with osteoporosis-related fractures and the same number of age- and sex-matched controls in never-smokers from the Swedish population-based Malmö Diet and Cancer study cohort. Cd in blood (B-Cd) was analyzed at baseline (1991-1996). Incident osteoporosis-related fractures (of the hip, distal radius, and proximal humerus) up to the year 2014 were identified using the National Patient Register. Associations between B-Cd and fractures were analyzed using logistic regression. RESULTS: Median B-Cd was 0.22 µg/L (P25 = 0.16, P75 = 0.31) among 2103 cases and 0.21 (P25 = 0.15, P75 = 0.30) among 2105 controls. The risk of fracture was significantly increased (OR 1.58; 95 % confidence interval 1.08-2.31, per µg/L of B-Cd), after adjustment for age, sex, BMI, physical activity, and fiber consumption. In analyses by cadmium quartiles, the OR increased monotonically and was significant in the highest quartile of B-Cd (for B-Cd > 0.31 versus B-Cd < 0.15 µg/L; OR 1.21; 95 % confidence interval 1.01-1.45). CONCLUSION: Even modestly increased blood cadmium in never-smokers is associated with increased risk of incident osteoporosis-related fractures.

Long-term exposure to traffic noise and risk of incident colon cancer: A pooled study of eleven Nordic cohorts.

Background Colon cancer incidence is rising globally, and factors pertaining to urbanization have been proposed involved in this development. Traffic noise may increase colon cancer risk by causing sleep disturbance and stress, thereby inducing known colon cancer risk-factors, e.g. obesity, diabetes, physical inactivity, and alcohol consumption, but few studies have examined this. Objectives The objective of this study was to investigate the association between traffic noise and colon cancer (all, proximal, distal) in a pooled population of 11 Nordic cohorts, totaling 155,203 persons. Methods We identified residential address history and estimated road, railway, and aircraft noise, as well as air pollution, for all addresses, using similar exposure models across cohorts. Colon cancer cases were identified through national registries. We analyzed data using Cox Proportional Hazards Models, adjusting main models for harmonized sociodemographic and lifestyle data. Results During follow-up (median 18.8 years), 2757 colon cancer cases developed. We found a hazard ratio (HR) of 1.05 (95% confidence interval (CI): 0.99-1.10) per 10-dB higher 5-year mean time-weighted road traffic noise. In sub-type analyses, the association seemed confined to distal colon cancer: HR 1.06 (95% CI: 0.98-1.14). Railway and aircraft noise was not associated with colon cancer, albeit there was some indication in sub-type analyses that railway noise may also be associated with distal colon cancer. In interaction-analyses, the association between road traffic noise and colon cancer was strongest among obese persons and those with high NO2-exposure. Discussion A prominent study strength is the large population with harmonized data across eleven cohorts, and the complete address-history during follow-up. However, each cohort estimated noise independently, and only at the most exposed façade, which may introduce exposure misclassification. Despite this, the results of this pooled study suggest that traffic noise may be a risk factor for colon cancer, especially of distal origin.

Occupational noise exposure and risk of incident stroke: a pooled study of five Scandinavian cohorts.

OBJECTIVES: To investigate the association between occupational noise exposure and stroke incidence in a pooled study of five Scandinavian cohorts (NordSOUND). METHODS: We pooled and harmonised data from five Scandinavian cohorts resulting in 78 389 participants. We obtained job data from national registries or questionnaires and recoded these to match a job-exposure matrix developed in Sweden, which specified the annual average daily noise exposure in five exposure classes (LAeq8h): <70, 70-74, 75-79, 80-84, ≥85 dB(A). We identified residential address history and estimated 1-year average road traffic noise at baseline. Using national patient and mortality registers, we identified 7777 stroke cases with a median follow-up of 20.2 years. Analyses were conducted using Cox proportional hazards models adjusting for individual and area-level potential confounders. RESULTS: Exposure to occupational noise at baseline was not associated with overall stroke in the fully adjusted models. For ischaemic stroke, occupational noise was associated with HRs (95% CI) of 1.08 (0.98 to 1.20), 1.09 (0.97 to 1.24) and 1.06 (0.92 to 1.21) in the 75-79, 80-84 and ≥85 dB(A) exposure groups, compared with <70 dB(A), respectively. In subanalyses using time-varying occupational noise exposure, we observed an indication of higher stroke risk among the most exposed (≥85 dB(A)), particularly when restricting analyses to people exposed to occupational noise within the last year (HR: 1.27; 95% CI: 0.99 to 1.63). CONCLUSIONS: We found no association between occupational noise and risk of overall stroke after adjustment for confounders. However, the non-significantly increased risk of ischaemic stroke warrants further investigation.

Using Distributed Lag Non-Linear Models to Estimate Exposure Lag-Response Associations between Long-Term Air Pollution Exposure and Incidence of Cardiovascular Disease.

Long-term air pollution exposure increases the risk for cardiovascular disease, but little is known about the temporal relationships between exposure and health outcomes. This study aims to estimate the exposure-lag response between air pollution exposure and risk for ischemic heart disease (IHD) and stroke incidence by applying distributed lag non-linear models (DLNMs). Annual mean concentrations of particles with aerodynamic diameter less than 2.5 µm (PM2.5) and black carbon (BC) were estimated for participants in five Swedish cohorts using dispersion models. Simultaneous estimates of exposure lags 1-10 years using DLNMs were compared with separate year specific (single lag) estimates and estimates for lag 1-5- and 6-10-years using moving average exposure. The DLNM estimated no exposure lag-response between PM2.5 total, BC, and IHD. However, for PM2.5 from local sources, a 20% risk increase per 1 µg/m3 for 1-year lag was estimated. A risk increase for stroke was suggested in relation to lags 2-4-year PM2.5 and BC, and also lags 8-9-years BC. No associations were shown in single lag models. Increased risk estimates for stroke in relation to lag 1-5- and 6-10-years BC moving averages were observed. Estimates generally supported a greater contribution to increased risk from exposure windows closer in time to incident IHD and incident stroke.

Incident cardiovascular disease and long-term exposure to source-specific air pollutants in a Swedish cohort.

BACKGROUND: Air pollution is associated with cardiovascular morbidity and mortality, but its role in the development of congestive heart failure (CHF) and the role of different pollution sources in cardiovascular disease remain uncertain. METHODS: Participants were enrolled in the Malmö Diet and Cancer cohort in 1991-1996 with information on lifestyle and clinical indicators of cardiovascular disease. The cohort participants were followed through registers until 2016. Annual total and local source-specific concentrations of particulate matter less than 10 µm and 2.5 µm (PM10 and PM2.5), black carbon (BC), and nitrogen oxides (NOx) from traffic, residential heating, and industry were assigned to each participant's address throughout the study period. Cox proportional hazards models adjusted for possible confounders was used to estimate associations between air pollution 1-5 years prior to outcomes of incident CHF, fatal myocardial infarction (MI), major adverse coronary events (MACE), and ischemic stroke. RESULTS: Air pollution exposure levels (mean annual exposures to PM2.5 of 11 µg/m3 and NOx of 26 µg/m3) within the cohort were moderate in terms of environmental standards. After adjusting for confounders, we observed statistically significant associations between NOx and CHF (hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.01-1.22) and NOx and fatal MI (HR 1.10, 95%CI 1.01-1.20) per interquartile range (IQR) of 9.6 µg/m3. In fully adjusted models, the estimates were similar, but the precision worse. In stratified analyses, the associations were stronger in males, ever-smokers, older participants, and those with baseline carotid artery plaques. Locally emitted and traffic-related air pollutants generally showed positive associations with CHF and fatal MI. There were no associations between air pollution and MACE or stroke. DISCUSSION/CONCLUSION: In an area with low to moderate air pollution exposure, we observed significant associations of long-term residential NOx with increased risk of incident CHF and fatal MI, but not with coronary events and stroke.

Associations between long-term exposure to low-level air pollution and risk of chronic kidney disease-findings from the Malmö Diet and Cancer cohort.

BACKGROUND: Associations between air pollution and chronic kidney disease (CKD) have been reported, but studies at low exposure levels and relevant exposure time windows are still warranted. This study investigated clinical CKD at low air pollution levels in the Swedish Malmö Diet and Cancer Cohort in different exposure time windows. METHODS: This study included 30,396 individuals, aged 45-74 at enrollment 1991-1996. Individual annual average residential outdoor PM2.5, PM10, nitrogen oxides (NOx), and black carbon (BC) were assigned using dispersion models from enrollment to 2016. Diagnoses of incident CKD were retrieved from national registries. Cox proportional hazards models were used to obtain hazard ratios (HRs) for CKD in relation to three time-dependent exposure time windows: exposure at concurrent year (lag 0), mean exposure in the 1-5 or 6-10 preceding years (lag 1-5 and lag 6-10), and baseline exposure. RESULTS: During the study period, the average annual residential exposures were 16 µg/m3 for PM10, 11 µg/m3 for PM2.5, 26 µg/m3 for NOx, and 0.97 µg/m3 for BC. For lag 1-5 and lag 6-10 exposure, significantly elevated HRs for incident CKD were found for total PM10:1.13 (95% CI: 1.01-1.26) and 1.22 (1.06-1.41); NOx: 1.19 (1.07-1.33) and 1.13 (1.02-1.25) and BC: 1.12 (1.03-1.22) and 1.11 (1.02-1.21) per interquartile range increase in exposure. For total PM2.5 the positive associations of 1.12 (0.97-1.31) and 1.16 (0.98-1.36) were not significant. For baseline or lag 0 exposure there were significant associations only for NOx and BC, not for PM. CONCLUSION: Residential exposure to outdoor air pollution was associated with increased risk of incident CKD at relatively low exposure levels. Average long-term exposure was more clearly associated with CKD than current exposure or exposure at recruitment. Our findings imply that the health effects of low-level air pollution on CKD are considerable.

Cancer incidence in a Swedish cohort with high exposure to perfluoroalkyl substances in drinking water.

BACKGROUND: The use of firefighting foams at a military airport resulted in high levels of perfluorinated substances (PFAS) in the drinking water distributed to one-third of households in the Swedish municipality of Ronneby between the mid-1980s and the end of 2013. METHOD: The Ronneby Register Cohort, a large cohort comprising all individuals (N = 60,507) who ever lived in the Ronneby municipality during the period of drinking water contamination, was linked to the Swedish Cancer Register 1985-2016. Individual exposure was classified based on comprehensive data on yearly residential address and water distribution. External analysis explored standardized cancer incidence ratios (SIR) for residents never, or ever, residing in the contaminated water district, compared with those residing in other towns in the same county as reference population. Cox models provided hazard ratios (HR) for different exposure groups within the cohort. RESULTS: 5,702 individuals with cancer were identified. SIR for overall cancer was 1.04 for men (95%CI 0.96-1.12) and 0.89 for women (95%CI 0.82-0.96) who ever lived in the contaminated drinking water area. Kidney cancer, which was reported with increased risk in C8 study, showed somewhat elevated HR in this study (HR 1.27; 95%CI 0.85-1.89). The HR was modestly elevated for bladder cancer (HR 1.32; 95%CI 1.01-1.72), and reduced for prostate cancer (HR 0.83; 95%CI 0.71-0.98). In subjects who ever lived in the contaminated water area during 2005-2013, when exposure was estimated to be highest, higher risks for kidney cancer (HR 1.84; 95%CI 1.00-3.37) but lower for prostate cancer (HR 0.76; 95%CI 0.59-0.98) were observed. CONCLUSION: Analysis of this large cohort exposed to high levels of PFAS, dominated by PFHxS and PFOS, revealed no evidence for an overall increased risk of cancer. A moderately increased risk of kidney cancer was observed, in accordance with previous findings after PFAS exposure dominated by PFOA.

Long-term exposure to particulate air pollution and black carbon in relation to natural and cause-specific mortality: a multicohort study in Sweden.

OBJECTIVES: To estimate concentration-response relationships for particulate matter (PM) and black carbon (BC) in relation to mortality in cohorts from three Swedish cities with comparatively low pollutant levels. SETTING: Cohorts from Gothenburg, Stockholm and Umeå, Sweden. DESIGN: High-resolution dispersion models were used to estimate annual mean concentrations of PM with aerodynamic diameter ≤10 µm (PM10) and ≤2.5 µm (PM2.5), and BC, at individual addresses during each year of follow-up, 1990-2011. Moving averages were calculated for the time windows 1-5 years (lag1-5) and 6-10 years (lag6-10) preceding the outcome. Cause-specific mortality data were obtained from the national cause of death registry. Cohort-specific HRs were estimated using Cox regression models and then meta-analysed including a random effect of cohort. PARTICIPANTS: During the study period, 7 340 cases of natural mortality, 2 755 cases of cardiovascular disease (CVD) mortality and 817 cases of respiratory and lung cancer mortality were observed among in total 68 679 individuals and 689 813 person-years of follow-up. RESULTS: Both PM10 (range: 6.3-41.9 µg/m3) and BC (range: 0.2-6.8 µg/m3) were associated with natural mortality showing 17% (95% CI 6% to 31%) and 9% (95% CI 0% to 18%) increased risks per 10 µg/m3 and 1 µg/m3 of lag1-5 exposure, respectively. For PM2.5 (range: 4.0-22.4 µg/m3), the estimated increase was 13% per 5 µg/m3, but less precise (95% CI -9% to 40%). Estimates for CVD mortality appeared higher for both PM10 and PM2.5. No association was observed with respiratory mortality. CONCLUSION: The results support an effect of long-term air pollution on natural mortality and mortality in CVD with high relative risks also at low exposure levels. These findings are relevant for future decisions concerning air quality policies.

Perfluoroalkyl substances (PFAS) in drinking water and risk for polycystic ovarian syndrome, uterine leiomyoma, and endometriosis: A Swedish cohort study.

BACKGROUND: Perfluorinated substances (PFAS) are chemicals with endocrine disruptive properties that may interfere with the female reproductive system. However, few studies have explored the association between benign gynecological diseases and high PFAS exposure. OBJECTIVES: The aim of this study was to investigate the possible associations between PFAS exposure and subsequent diagnosis of polycystic ovarian syndrome (PCOS), uterine leiomyoma (fibroids), and endometriosis in a cohort exposed to PFAS through drinking water. MATERIAL AND METHODS: In 2013, high levels (with sum of PFAS above 10,000 ng/L), dominated by perfluorooctanesulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS), were found in the drinking water from one of the two waterworks in Ronneby, Sweden. The contamination came from firefighting foams used at a nearby airfield. Females of all ages (n = 29,106) who had ever resided in the municipality between 1985 and 2013 formed a cohort. Individual exposure was assessed based on municipality waterworks distribution data linked to annual residential address data; 27% of the females had ever lived at an address with PFAS-contaminated water. Gynecological health outcomes were retrieved from the Swedish National Patient Register. The Cox proportional hazards model was used to estimate the association between exposure and each diagnosis. RESULTS: There were in all 161 cases of PCOS, 1,122 cases of uterine leiomyoma, and 373 cases of endometriosis. In women aged 20-50 years (n = 18,503), those with the highest estimated PFAS exposure had increased hazard ratios (HR) for PCOS (HR = 2.18; 95% confidence interval (CI) 1.43, 3.34) and uterine leiomyoma (HR = 1.28; 95% CI 0.95, 1.74). No increased HR for endometriosis was found (HR = 0.74; 95% CI 0.42, 1.29). CONCLUSIONS: Exposure to high levels of PFAS in drinking water was associated with increased risk of PCOS and possibly uterine leiomyoma, but not endometriosis. The findings for PCOS are consistent with prior studies reporting positive associations between PCOS and PFAS exposure at background levels.

Is Cadmium a Risk Factor for Breast Cancer - Results from a Nested Case-Control Study Using Data from the Malmö Diet and Cancer Study.

BACKGROUND: Some studies have shown that cadmium (Cd) is associated with breast cancer risk. One hypothesis is that Cd has estrogen-like properties. This case-control study investigated the association between breast cancer risk and blood Cd (BCd) levels. METHODS: All breast cancers in the Malmö Diet and Cancer cohort were identified through linkage to the Swedish Cancer Registry, baseline (1991-1996) through 2014. Two controls per case were selected from the same cohort. BCd was analyzed at baseline. Associations were analyzed using logistic regression. RESULTS: Mean BCd was 0.51 µg/L among 1,274 cases and 0.46 among 2,572 controls. There was an overall increased risk of breast cancer [OR, 1.18; 95% confidence interval (CI), 1.05-1.36] per µg/L of BCd. An increased risk was, however, only found at high BCd [OR, 1.34 (95% CI, 1.05-1.73)] for BCd more than 1.20 µg/L. The group with the highest BCd was mainly smokers. A spline indicated that at BCd less than 1.0 µg/L, the OR was not increased. The association with BCd was stronger in current smokers and at body mass index (BMI) above 25, while no modification due to receptor status was found. CONCLUSIONS: The results indicated increased risk of breast cancer only for high Cd exposure, which occurred mainly among smokers. This made it difficult to disentangle the effects of smoking and Cd, despite inclusion of smoking habits in the models. IMPACT: This study provides support for reducing Cd exposure through smoking cessation and dietary choice. On the population level, preventive measures against Cd pollution are warranted.

Cadmium Exposure and Coronary Artery Atherosclerosis: A Cross-Sectional Population-Based Study of Swedish Middle-Aged Adults.

BACKGROUND: The general population is ubiquitously exposed to the toxic metal cadmium through the diet and smoking. Cadmium exposure is associated with increased morbidity and mortality in myocardial infarction and stroke. Atherosclerosis is the main underlying mechanism of myocardial infarction. However, associations between cadmium and coronary artery atherosclerosis have not been examined. OBJECTIVES: Our study sought to examine the hypothesis that blood cadmium (B-Cd) is positively associated with coronary artery calcification, as a measure of coronary artery atherosclerosis in the population-based Swedish SCAPIS study. METHODS: Our analysis included 5,627 individuals (51% women), age 50-64 y, enrolled from 2013 to 2018. The coronary artery calcium score (CACS) was obtained from computed tomography. Blood cadmium was determined by inductively coupled plasma mass spectrometry (ICP-MS). Associations between B-Cd and coronary artery calcium score (CACS Agatston score) were evaluated using prevalence ratios (PRs) in models adjusted for sex, age, smoking, hypertension, diabetes, low-density cholesterol/high-density cholesterol ratio, and family history. RESULTS: The median B-Cd concentration was 0.24µg/L. The prevalence of positive coronary artery calcium (CACS>0) was 41% and the prevalence of CACS≥100 was 13%. Relative to the lowest quartile (Q) of B-Cd (<0.16µg/L), the highest quartile (median 0.63µg/L) was associated with a small but significant increase in CACS>0 (PR 1.1; 95% CI: 1.0, 1.3), and a greater relative increase in CACS≥100 (PR 1.6; 95% CI: 1.3, 2.0). When restricted to 2,446 never-smokers, corresponding PRs were 1.1 (95% CI 0.9, 1.3) for CACS>0 (63 cases in Q4) and 1.7 (95% CI 1.1, 2.7) for CACS≥100 (17 cases in Q4). DISCUSSION: Blood cadmium in the highest quartile was associated with CACS in a general population sample with low to moderate cadmium exposure. This supports the hypothesis that atherosclerosis is an important mechanism underlying the associations between cadmium and incident cardiovascular disease. The findings suggest that public health measures to reduce cadmium exposure are warranted. https://doi.org/10.1289/EHP8523.

Cadmium, total mercury, and lead in blood and associations with diet, sociodemographic factors, and smoking in Swedish adolescents.

BACKGROUND: Despite their vulnerability to the toxic effects of certain metals, biomonitoring data on adolescents are limited. In the present study, we assessed blood concentrations of toxic metals (cadmium [Cd], total mercury [Hg], and lead [Pb] in a national representative sample of Swedish adolescents. We also examined the associations of Cd, total Hg and Pb with habitual intakes of major energy-providing food groups and other possible determinants such as age, sex, household education, Nordic or non-Nordic origin, and smoking. METHODS: We analysed blood concentrations of Cd, total Hg, and Pb in a sample of 1099 adolescents from the Riksmaten Adolescents 2016-17 study in three age groups (mean age of 12, 15, and 18 years) using inductively coupled plasma mass spectrometry. The participants completed web-based questionnaires on food consumption frequency, sociodemographic factors and health status. Dietary data from two web-based 24-h dietary recalls were used to estimate the habitual intake of 10 major food groups. RESULTS: Almost all participants had detectable concentrations of Cd, total Hg, and Pb in whole blood. The median blood concentrations were 0.12 µg/L for Cd, 0.72 µg/L for total Hg, and 7.1 µg/L for Pb. Higher blood concentrations of Cd were observed in girls than in boys, whereas concentrations of total Hg and Pb were higher in boys. We observed an inverse association between Cd and meat intake. Total Hg concentrations were positively associated with intakes of fish, eggs, meat, and vegetables, and Pb concentrations were inversely associated with intakes of dairy products. Furthermore, smokers had higher concentrations of Cd and Pb. CONCLUSIONS: We found that fish was a potentially important source of exposure to total Hg in Swedish adolescents. No other food group was identified to have a strong impact on the blood levels of Cd, total Hg and Pb. Thirteen per cent of the adolescents had blood Pb concentrations above 12 µg/L, the reference point used in the risk assessment of Pb by the European Food Safety Authority (EFSA).

Long-term exposure to air pollution and atherosclerosis in the carotid arteries in the Malmö diet and cancer cohort.

BACKGROUND: Long-term exposure to air pollution increases the risk of cardiovascular morbidity and mortality, but the mechanisms are not fully known. Current evidence suggests that air pollution exposure contributes to the development of atherosclerosis. There are few studies investigating associations between air pollution and carotid plaques, a well-known precursor of cardiovascular disease. METHODS: A Swedish population-based cohort (aged 45-64 years at recruitment) was randomly selected from the Malmö Diet and Cancer study between 1991 and 1994, of which 6103 participants underwent ultrasound examination of the right carotid artery to determine carotid plaque presence and carotid intima media thickness (CIMT). Participants were assigned individual residential air pollution exposure (source-specific PM2.5, PM10, NOx, BC) at recruitment from Gaussian dispersion models. Logistic and linear regression models, adjusted for potential confounders and cardiovascular risk factors, were used to investigate associations between air pollutants and prevalence of carotid plaques, and CIMT, respectively. RESULTS: The prevalence of carotid plaques was 35%. The mean levels of PM2.5 and PM10 at recruitment were 11 and 14 µg/m3, most of which was due to long range transport. The exposure contrast within the cohort was relatively low. PM2.5 exposure was associated with carotid plaques in a model including age and sex only (OR 1.10 (95% CI 1.01-1.20) per 1 µg/m3), but after adjustment for cardiovascular risk factors and socioeconomic status (SES) the association was weak and not significant (OR 1.05 (95% CI 0.96-1.16) per 1 µg/m3). The pattern was similar for PM10 and NOx exposure. Associations between air pollutants and plaques were slightly stronger for long-term residents and in younger participants with hypertension. There was no clear linear trend between air pollution exposure and plaque prevalence. Non-significant slightly positive associations were seen between air pollution exposures and CIMT. CONCLUSIONS: In this large, well-controlled cross-sectional study at low exposure levels we found no significant associations between air pollution exposures and subclinical atherosclerosis in the carotid arteries, after adjusting for cardiovascular risk factors and SES. Further epidemiological studies of air pollution and intermediate outcomes are needed to explain the link between air pollution and cardiovascular events.

Smoking-Induced Risk of Osteoporosis Is Partly Mediated by Cadmium From Tobacco Smoke: The MrOS Sweden Study.

Cigarette smoking is a risk factor for osteoporosis and bone fracture. Moreover, smoking causes exposure to cadmium, which is a known risk factor for osteoporosis. It is hypothesized that part of smoking-induced osteoporosis may be mediated via cadmium from tobacco smoke. We investigated this hypothesis using mediation analysis in a Swedish cohort of elderly men. This study was performed in 886 elderly men from the Swedish cohort of the Osteoporotic Fractures in Men (MrOS) study. Urinary samples, bone mineral density (BMD), smoking data, and other background information were obtained at baseline in 2002-2004. Urinary cadmium was analyzed in baseline samples and adjusted for creatinine. The cohort was followed until August 2018 for fracture incidence, based on the X-ray register. Mediation analysis was conducted to evaluate the indirect effect (via cadmium) of smoking on both BMD and fractures. Time to first fracture was analyzed using the accelerated failure time (AFT) model and Aalen's additive hazard model. The mean level of urinary cadmium was 0.25 µg/g creatinine. There were significant inverse associations between smoking and total body, total hip, and trochanter BMD. The indirect effects via cadmium were estimated to be 43% of the total effects of smoking for whole-body BMD, and even more for total hip and trochanter BMD. Smoking was also associated with higher risk of all fractures and major osteoporosis fractures. The indirect effects via cadmium were largest in nonvertebral osteoporosis fractures and hip fractures, constituting at least one-half of the total effects, in both the AFT and Aalen's model. The findings in this study provide evidence that cadmium exposure from tobacco smoke plays an important role in smoking-induced osteoporosis © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Smoking-induced risk of future cardiovascular disease is partly mediated by cadmium in tobacco: Malmö Diet and Cancer Cohort Study.

BACKGROUND: Smoking is a strong risk factor for cardiovascular disease (CVD) and causes exposure to cadmium, which is a pro-atherosclerotic metal. Cadmium exposure has also been shown to increase the risk of CVD, even after adjustment for smoking. Our hypothesis was that part of the risk of CVD in smokers may be mediated by cadmium exposure from tobacco smoke. We examined this hypothesis in a mediation analysis, trying to assess how much of the smoking-induced CVD risk could be explained via cadmium. METHODS: We used prospective data on CVD (incidence and mortality) in a Swedish population-based cohort of 4304 middle-aged men and women (the Malmö Diet and Cancer Study). Blood cadmium was analyzed in base-line samples from 1991, and clinical events were followed up for 16-19 years based on registry data. Mediation analysis was conducted to evaluate the indirect effect (via cadmium) of smoking on CVD. Survival was analyzed by the accelerated failure time (AFT) model and the Aalen additive hazard model. RESULTS: The mean blood cadmium level in the study population was 0.43 µg/L (median 0.24 µg/L) and increased with recent and current smoking. As expected, shorter survival time (AFT model) and higher incidence rate (Aalen model) were found in current smokers for all CVD outcomes and this effect seemed to be partly mediated by cadmium. For the sum of acute myocardial infarction, bypass grafts and percutaneous coronary intervention, and death in ischemic heart disease, about half of the increased risk of such events in current smokers was mediated via cadmium, with similar results for the AFT and Aalen models. CONCLUSIONS: Cadmium plays an important role in smoking-induced CVDs. This provides evidence for mechanisms and is of importance for both individuals and policy makers.

Partial Mediation by Cadmium Exposure of the Association Between Tobacco Smoking and Atherosclerotic Plaques in the Carotid Artery.

Exposure to cadmium confers increased cardiovascular risk. Tobacco smoke contains cadmium, which, hypothetically, may mediate parts of the tobacco-associated risk of developing atherosclerotic plaques. Baseline data from the Swedish Malmö Diet and Cancer cohort (1991-1996) were used to test this hypothesis. Mediation analysis was used to examine associations between smoking and blood cadmium levels and the prevalence of ultrasound-assessed carotid atherosclerotic plaques. The total association with smoking status (never smokers, 2 categories of former smokers, and current smokers) was split into direct and indirect association, and the proportion mediated was estimated. The adjusted estimated plaque prevalence was approximately 27% among never smokers. We identified both a direct and an indirect pathway between smoking and carotid plaques; the indirect association, through cadmium, was observed among current smokers and former smokers who had quit smoking less than 15 years before. For current smokers, the prevalence ratio for plaque was 1.5, with 60%-65% of the association with smoking being mediated through cadmium. Recent former smokers had a prevalence ratio of 1.3, and 40%-45% was mediated through cadmium. Long-time former smokers had a prevalence ratio of 1.2, but none of the association was mediated through cadmium. In conclusion, about two-thirds of the proatherosclerotic association with smoking was mediated by cadmium.

Lung cancer risk from radon exposure in dwellings in Sweden: how many cases can be prevented if radon levels are lowered?

PURPOSE: Residential exposure to radon is considered to be the second cause of lung cancer after smoking. The purpose of this study was to estimate the number of lung cancer cases prevented from reducing radon exposure in Swedish dwellings. METHODS: Measurements of indoor radon are available from national studies in 1990 and 2008 with 8992 and 1819 dwellings, considered representative of all Swedish dwellings. These data were used to estimate the distribution of radon in Swedish dwellings. Lung cancer risk was assumed to increase by 16% per 100 becquerels per cubic meter (Bq/m(3)) indoor air radon. Estimates of future and saved cases of lung cancer were performed at both constant and changed lung cancer incidence rates over time. RESULTS: The arithmetic mean concentration of radon was 113 Bq/m(3) in 1990 and 90 Bq/m(3) in 2008. Approximately 8% of the population lived in houses with >200 Bq/m(3). The estimated current number of lung cancer cases attributable to previous indoor radon exposure was 591 per year, and the number of future cases attributable to current exposure was 473. If radon levels above 100 Bq/m(3) are lowered to 100 Bq/m(3), 183 cases will be prevented. If levels >200 Bq/m(3) are lowered to 140 Bq/m(3) (mean in the present stratum 100-200 Bq/m(3)), 131 cases per year will be prevented. CONCLUSIONS: Although estimates are somewhat uncertain, 35-40% of the radon attributed lung cancer cases can be prevented if radon levels >100 Bq/m(3) are lowered to 100 Bq/m(3).

The effect of secondary inorganic aerosols, soot and the geographical origin of air mass on acute myocardial infarction hospitalisations in Gothenburg, Sweden during 1985-2010: a case-crossover study.

BACKGROUND: The relative importance of different sources of air pollution for cardiovascular disease is unclear. The aims were to compare the associations between acute myocardial infarction (AMI) hospitalisations in Gothenburg, Sweden and 1) the long-range transported (LRT) particle fraction, 2) the remaining particle fraction, 3) geographical air mass origin, and 4) influence of local dispersion during 1985-2010. METHODS: A case-crossover design was applied using lag0 (the exposure the same day as hospitalisation), lag1 (exposure one day prior hospitalisation) and 2-day cumulative average exposure (CA2) (mean of lag0 and lag1). The LRT fractions included PMion (sum of sulphate, nitrate and ammonium) and soot measured at a rural site. The difference between urban PM10 (particulate matter with an aerodynamic diameter smaller than 10 µm) and rural PMion was a proxy for locally generated PM10 (PMrest). The daily geographical origin of air mass was estimated as well as days with limited or effective local dispersion. The entire year was considered, as well as warm and cold periods, and different time periods. RESULTS: In total 28 215 AMI hospitalisations occurred during 26 years. PM10, PMion, PMrest and soot did not influence AMI for the entire year. In the cold period, the association was somewhat stronger for PMrest than for urban PM10; the strongest associations were observed during 1990-2000 between AMI and CA2 of PMrest (6.6% per inter-quartile range (IQR), 95% confidence interval 2.1 to 11.4%) and PM10 (4.1%, 95% CI 0.2% - 8.2%). Regarding the geographical air mass origins there were few associations. Days with limited local dispersion showed an association with AMI in the cold period of 2001-2010 (6.7%, 95% CI 0.0% - 13.0%). CONCLUSIONS: In the cold period, locally generated PM and days with limited local dispersion affected AMI hospitalisations, indicating importance of local emissions from e.g. traffic.

Determinants of personal exposure to some carcinogenic substances and nitrogen dioxide among the general population in five Swedish cities.

Environmental levels of airborne carcinogenic and related substances are comparatively better known than individual exposure and its determinants. We report on a personal monitoring program involving five Swedish urban populations. The aim of the program was to investigate personal exposure to benzene, 1,3-butadiene, formaldehyde, and nitrogen dioxide (NO2). The measurements were performed among 40 inhabitants during seven consecutive days, in one urban area each year, during 2000-2008. The estimated population exposure levels were 1.95 µg/m(3) for benzene, 0.56 µg/m(3) for 1,3-butadiene, 19.4 µg/m(3) for formaldehyde, and 14.1 µg/m(3) for NO2. Statistical analysis using a mixed-effects model revealed that time spent in traffic and time outdoors contributed to benzene and 1,3- butadiene exposure. For benzene, refueling a car was an additional determinant influencing the exposure level. Smoking or environmental tobacco smoke were significant determinants of exposure to NO2, benzene, and 1,3-butadiene. Those with a gas stove had higher NO2 exposure. Living in a single-family house increased the exposure to formaldehyde significantly. In a variance component model, the between-subject variance dominated for 1,3-butadiene and formaldehyde, whereas the between-city variance dominated for NO2. For benzene, the between-subject and between-cities variances were similar.