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.

Exposure to high levels of PFAS through drinking water is associated with increased risk of type 2 diabetes-findings from a register-based study in Ronneby, Sweden.

BACKGROUND: Epidemiological studies linking type 2 diabetes (T2D) and exposure to per- and polyfluoroalkyl substances (PFAS), are limited and have yielded conflicting results. This register-based study aimed to investigate the risk of T2D among Swedish adults who had been exposed to PFAS from highly contaminated drinking water for decades. METHODS: The study included 55,032 adults (aged ≥18 years) from the Ronneby Register Cohort, who ever lived in Ronneby during 1985-2013. Exposure was assessed using the yearly residential address and the absence ("never-high") or presence ("ever-high") of high PFAS contamination in the municipal drinking water supply; the latter was subdivided into "early-high" and "late-high" exposure with cut-off at 2005. Incident T2D cases were retrieved from the National Patient Register and the Prescription Register. Cox proportional hazard models with time-varying exposure were used to estimate hazard ratios (HRs). Stratified analyses were performed based on age (18-45 vs > 45). RESULTS: Elevated HRs for T2D were observed when comparing "ever-high" to "never-high" exposure (HR 1.18, 95% CI 1.03-1.35), as well as when comparing "early-high" (HR 1.12, 95% CI 0.98-1.50) or "late-high" (HR 1.17, 95% CI 1.00-1.37) to "never-high", after adjusting for age and sex. Individuals aged 18-45 years had even higher HRs. Adjusting for the highest-achieved education level attenuated the estimates, but the directions of associations remained. Elevated HRs were also found among those who had lived in areas with a heavily contaminated water supply for 1-5 years (HR 1.26, 95% CI 0.97-1.63) and 6-10 years (HR 1.25, 95% CI 0.80-1.94). CONCLUSION: This study suggests an increased risk of T2D after long-term high PFAS exposure through drinking water. In particular, a higher risk of early onset diabetes was found, indicating increased susceptibility to PFAS-related health effects at younger ages.

High exposure to perfluoroalkyl substances in drinking water is associated with increased risk of osteoporotic fractures - A cohort study from Ronneby, Sweden.

BACKGROUND: Perfluoroalkyl substances (PFAS) have been reported to be related to decreased bone mineral density, but the relationship with osteoporosis and fractures is less studied. This study aimed to investigate the risks of osteoporotic fractures in a Swedish population with long-term exposure to PFAS through drinking water. METHODS: The Ronneby Register Cohort, including 61,504 individuals who had ever lived in Ronneby during 1985-2013, was used. Exposure to PFAS was assessed according to the yearly residential address with or without highly contaminated water supply and was categorized as 'never-high' and 'ever-high' exposure. The 'ever-high' exposure was further divided into 'early-high' and 'late-high' depending on if the exposure was before or after 2005. Inpatient and outpatient hospital diagnoses of fractures were retrieved from the National Patient Register. Major osteoporotic fractures (MOF, i.e., hip, vertebrae, proximal humerus and distal forearm fractures), and hip fractures were considered as the primary outcomes. Cox proportional hazard models with time-varying exposure were used to estimate the hazard ratios (HRs). Stratified analyses were performed in each sex and age group (<50 yrs and ≥ 50 yrs). RESULTS: Elevated risks of MOF (HR 1.11, 95% CI 1.03-1.19) and hip fractures (1.12, 1.00-1.24) were observed when comparing 'ever-high' to 'never-high' exposure. The HRs were even higher for 'late-high' exposure (MOF: 1.29, 1.16-1.44; hip fractures: 1.22, 1.01-1.47). Further adjustment for highest achieved education slightly attenuated the estimates. Individuals above 50 years old showed even higher HR estimates. Similar patterns were found for all fractures. CONCLUSION: Our results provide further evidence supporting the adverse effects of PFAS on osteoporosis. A better understanding of dose-response relationships as a basis for risk assessment is warranted.

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.

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.

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 air pollution, coronary artery calcification, and carotid artery plaques in the population-based Swedish SCAPIS Gothenburg cohort.

Long-term exposure to air pollution is associated with cardiovascular events. A main suggested mechanism is that air pollution accelerates the progression of atherosclerosis, yet current evidence is inconsistent regarding the association between air pollution and coronary artery and carotid artery atherosclerosis, which are well-established causes of myocardial infarction and stroke. We studied associations between low levels of long-term air pollution, coronary artery calcium (CAC) score, and the prevalence and area of carotid artery plaques, in a middle-aged population-based cohort. The Swedish CArdioPulmonary bioImage Study (SCAPIS) Gothenburg cohort was recruited during 2013-2017 and thoroughly examined for cardiovascular risk factors, including computed tomography of the heart and ultrasonography of the carotid arteries. In 5070 participants (age 50-64 years), yearly residential exposures to air pollution (PM2.5, PM10, PMcoarse, NOx, and exhaust-specific PM2.5 1990-2015) were estimated using high-resolution dispersion models. We used Poisson regression to examine associations between long-term (26 years' mean) exposure to air pollutants and CAC score, and prevalence of carotid artery plaques, adjusted for potential confounders. Among participants with carotid artery plaques, we also examined the association with plaque area using linear regression. Mean exposure to PM2.5 was low by international standards (8.5 µg/m3). There were no consistent associations between long-term total PM2.5 exposure and CAC score or presence of carotid artery plaques, but an association between total PM2.5 and larger plaque area in participants with carotid plaques. Associations with traffic-related air pollutants were consistently positive for both a high CAC score and bilateral carotid artery plaques. These associations were independent of road traffic noise. We found stronger associations among men and participants with cardiovascular risk factors. The results lend some support to atherosclerosis as a main modifiable pathway between low levels of traffic-related ambient air pollution and cardiovascular disease, especially in vulnerable individuals.

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).

Associations between perfluoroalkyl substances and thyroid hormones after high exposure through drinking water.

BACKGROUND: The reported associations for several per- and polyfluoroalkyl substance (PFAS) with thyroid hormones are inconsistent in epidemiological studies. The purpose of the current study was to investigate the possible association of thyroid hormones in relation to serum levels of perfluorohexane sulfonate, perfluorooctane sulfonate and perfluorooctanoic acid, in a Swedish general population, highly exposed through contaminated drinking water, and if the associations with PFAS remained in a comparison to a reference group based only on residency in areas with contrasting PFAS levels. METHOD: 3297 participants from Ronneby, a municipality with drinking water highly contaminated by PFAS (exposed group), and a reference group (N = 226) from a nearby municipality with non-contaminated drinking water supply were included. Regression analysis was used to investigate the associations between PFAS exposure, assessed as exposure groups (Ronneby and reference groups) and measured serum PFAS levels, and thyroid hormone levels, with adjustments for age, sex and BMI. RESULT: No cross-sectional associations were found between PFAS and thyroid hormones in adults and seniors except for a positive association between PFAS and fT4 in males over 50. Higher thyroid hormone levels were found in the preteen children from Ronneby compared to the reference group. In contrast, within Ronneby, there was weak evidence of associations between increased PFAS levels and decreased fT3 in preteen boys, and decreased TSH in teenage males. No such pattern was found in preteen and teenage girls. CONCLUSION: The present study found no consistent evidence to support association of PFAS with thyroid hormones.

Road traffic noise, air pollution and cardiovascular events in a Swedish cohort.

Urbanization and increasing road traffic cause exposure to both noise and air pollution. While the levels of air pollutants such as nitrogen oxides (NOx) have decreased in Sweden during the past decades, exposure to traffic noise has increased. The association with cardiovascular morbidity is less well established for noise than for air pollution, and most studies have only studied one of the two highly spatially correlated exposures. The Swedish Primary Prevention Study cohort consists of men aged 47 to 55 when first examined in 1970-1973. The cohort members were linked to the Swedish patient registry through their personal identity number and followed until first cardiovascular event 1970-2011. The address history during the entire study period was used to assign annual modelled residential exposure to road traffic noise and NOx. The Cox proportional hazards model with age on the time axis and time-varying exposures were used in the analysis. The results for 6304 men showed a non-significant increased risk of cardiovascular disease for long-term road traffic noise at the home address, after adjusting for air pollution. The hazard ratios were 1.08 (95% CI 0.90-1.28) for cardiovascular mortality, 1.14 (95% CI 0.96-1.36) for ischemic heart disease incidence and 1.07 (95% CI 0.85-1.36) for stroke incidence, for noise above 60 dB, compared to below 50 dB. This study found some support for cardiovascular health effects of long-term exposure to road traffic noise above 60 dB, after having accounted for exposure to air pollution.

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.

Inflammatory bowel disease and biomarkers of gut inflammation and permeability in a community with high exposure to perfluoroalkyl substances through drinking water.

Perfluoroalkyl substances (PFAS) can act as surfactants and have been suggested to be capable of affecting gut mucosa integrity, a possible factor in the pathogenesis of inflammatory bowel disease (IBD). So far, only PFOA has been shown to have a positive association with ulcerative colitis. The present study aimed to investigate the association of PFAS and clinically diagnosed IBD in the Ronneby cohort, a population with high PFAS exposure (especially high PFOS and PFHxS) from Aqueous Film-Forming Foam through drinking water, using registry data. Additionally, to explore associations of PFAS with fecal zonulin and calprotectin, subclinical biomarkers of gut inflammation and permeability, in a sub-set of participants from Ronneby and Karlshamn (a nearby control municipality). The registry study included all people that ever resided in Ronneby municipality at least one year between 1980 and 2013. Yearly exposure to contaminated drinking water was assessed based on residential addresses and waterworks supply data, and the population classified by early, mid and late periods in ascending level of contamination. Diagnosed IBD cases were retrieved from the Swedish National Patient register and cause-of-death register. The Cox proportional hazards model was used to derive the hazard ratios (HRs) for diagnosed IBD. The biomarker study included 189 individuals who provided fecal samples. Serum PFAS were measured using LC-MS/MS. Fecal zonulin and calprotectin were measured using ELISA. Linear regression was used to assess the associations between measured PFAS and biomarker levels. In the registry study, no raised HRs for diagnosed IBD were found for cohort subjects with mid (1995-2004) or late period (2005-2013) exposure compared to never exposure. Early period exposure only (1985-1994) showed raised HRs for Crohn's disease (HR = 1.58, p = 0.048) and other non-specified IBD (HR = 1.38, p = 0.037). In the biomarker study, Karlshamn showed higher fecal calprotectin levels (median = 99.6 mg/kg in Karlshamn vs. 66.8 mg/kg in Ronneby, p = 0.04). A trend of decreased calprotectin with increased serum PFAS indicated higher PFAS was associated with lower degree of gut inflammation (p = 0.002). No association between serum PFAS and fecal zonulin was found. In conclusion, the present study found no consistent evidence to support PFAS exposure as a risk factor for IBD.

High exposure to perfluorinated compounds in drinking water and thyroid disease. A cohort study from Ronneby, Sweden.

Per- and polyfluoroalkyl substances (PFAS) are extremely persistent manmade substances. Apart from exposure through food and indoor air and dust, humans can be exposed through drinking water if the surface or groundwater is contaminated. In 2013 very high levels of PFOS and PFHxS were found in the drinking water from one of the two waterworks supplying the municipality of Ronneby, Sweden. A cohort was formed, including all individuals who had lived at least one year in Ronneby during the period 1980-2013 (ñ63,000). Each year, addresses that got their drinking water from the contaminated water works were identified. Through the Swedish personal identity number, each individual was linked to registers providing diagnoses and prescriptions for hyper- and hypothyroidism. In total, 16,150 individuals had ever been exposed. The hazard ratios did not indicate any excess risk of hyperthyroidism among those with contaminated water. For hypothyroidism, the risk of being prescribed medication was significantly increased among women with exposure during the mid part of the study period (but not men). However, the association with period of exposure was non-monotonic, so the significance is considered to be a chance finding. Our research was limited by the relatively simple exposure assessment.

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.

Long-term effects of total and source-specific particulate air pollution on incident cardiovascular disease in Gothenburg, Sweden.

BACKGROUND AND AIMS: Long-term exposure to air pollution increases cardiopulmonary morbidity and mortality, but it is not clear which components of air pollution are the most harmful, nor which time window of exposure is most relevant. Further studies at low exposure levels have also been called for. We analyzed two Swedish cohorts to investigate the effects of total and source-specific particulate matter (PM) on incident cardiovascular disease for different time windows of exposure. METHODS: Two cohorts initially recruited to study predictors of cardiovascular disease (the PPS cohort and the GOT-MONICA cohort) were followed from 1990 to 2011. We collected data on residential addresses and assigned each individual yearly total and source-specific PM and Nitrogen Oxides (NOx) exposures based on dispersion models. Using multivariable Cox regression models with time-dependent exposure, we studied the association between three different time windows (lag 0, lag 1-5, and exposure at study start) of residential PM and NOx exposure, and incidence of ischemic heart disease, stroke, heart failure and atrial fibrillation. RESULTS AND DISCUSSION: During the study period, there were 2266 new-onset cases of ischemic heart disease, 1391 of stroke, 925 of heart failure and 1712 of atrial fibrillation. The majority of cases were in the PPS cohort, where participants were older. Exposure levels during the study period were moderate (median: 13µg/m3 for PM10 and 9µg/m3 for PM2.5), and similar in both cohorts. Road traffic and residential heating were the largest local sources of PM air pollution, and long distance transportation the largest PM source in total. In the PPS cohort, there were positive associations between PM in the last five years and both ischemic heart disease (HR: 1.24 [95% CI: 0.98-1.59] per 10µg/m3 of PM10, and HR: 1.38 [95% CI: 1.08-1.77] per 5µg/m3 of PM2.5) and heart failure. In the GOT-MONICA cohort, there were positive but generally non-significant associations between PM and stroke (HR: 1.48 [95% CI: 0.88-2.49] per 10µg/m3 of PM10, and HR: 1.50 [95% CI: 0.90-2.51] per 5µg/m3 of PM2.5, in the last five years). Effect estimates were stronger for women, non-smokers, and higher socioeconomic classes. Exposure in the last five years seemed to be more strongly associated with outcomes than other exposure time windows. Associations between source-specific PM air pollution and outcomes were mixed and generally weak. High correlations between the main pollutants limited the use of multi-pollutant models. CONCLUSIONS: The main PM air pollutants were associated with ischemic heart disease and stroke (in women) at the relatively low exposure levels in Gothenburg, Sweden. The associations tended to be stronger for women than for men, for non-smokers than for smokers, and for higher socioeconomic classes than for lower. The associations could not be attributed to a specific PM source or type, and differed somewhat between the two cohorts. The results of this study confirm that further efforts to reduce air pollution exposure should be undertaken in Sweden to reduce the negative health effects in the general population.

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).

Long term effects of residential NO(x) exposure on total and cause-specific mortality and incidence of myocardial infarction in a Swedish cohort.

BACKGROUND AND AIMS: Exposure to air pollution has been linked to total and cardiopulmonary mortality. However, few studies have examined the effects of exposure over decades, or which time windows of long term exposure are most relevant. We investigated the long term effects of residential air pollution on total and cause-specific mortality and incidence of myocardial infarction in a well-characterized cohort of men in Sweden. METHODS: A cohort of 7494 men in Gothenburg was examined in 1970-1973 and followed subsequently to determine predictors of cardiovascular disease. We collected data on residential address and cause-specific mortality for the years 1973-2007. Each individual was assigned yearly nitrogen oxides (NOx) exposure based on dispersion models. Using multivariable Cox regression and generalized additive models with time-dependent exposure, we studied the association between three different time windows of residential NOx exposure, and selected outcomes. RESULTS: In the years 1973-2007, a total of 5669 deaths, almost half of which were due to cardiovascular diseases, occurred in the cohort. Levels of NOx exposure decreased during the study period, from a median of 38 µg/m(3) in 1973 to 17 µg/m(3) in 2007. Total non-accidental mortality was associated with participants' NOx exposure in the last year (the year of outcome) (HR 1.03, 95% CI 1.01-1.05, per 10 µg/m(3)), with the mean NOx exposure during the last 5 years, and with the mean NOx exposure since enrolment (HR 1.02, 95% CI 1.01-1.04 for both). The associations were similar (HR 1.01-1.03), but generally not statistically significant, for cardiovascular, ischemic heart disease, and acute myocardial infarction mortality, and weaker for cerebrovascular and respiratory mortality. There was no association between NOx exposure and incident myocardial infarction. DISCUSSION AND CONCLUSIONS: Long term residential exposure to NOx at these relatively low exposure levels in Gothenburg was associated with total non-accidental mortality. The association was as strong for NOx exposure in the last year as for longer exposure windows. The effect was near linear, and only marginally affected by confounders and effect modifiers. The improved air quality in Gothenburg has by these estimates led to a 6% decrease in excess non-accidental mortality during the study period.

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.