Low-level exposure to lead and atherosclerosis in the carotid arteries: Results from the Swedish population-based cohort SCAPIS.

BACKGROUND: Lead exposure is associated with cardiovascular disease. Atherosclerosis has been hypothesized to be one of the underlying mechanisms behind this association. AIM: To investigate whether lead exposure is associated with an increased risk of atherosclerosis in the carotid arteries in a large Swedish population-based cohort. METHODS: We performed a cross-sectional study using data from the population-based Swedish CardioPulmonary bioImage Study (SCAPIS), including 5622 middle-aged men and women, enrolled 2013-2018. Blood lead (B-Pb), measured by inductively coupled plasma mass spectrometry, was used as exposure biomarker. The presence of atherosclerotic plaque in the carotid arteries (yes/no), total plaque area (mm2) and the presence of large plaques (>25 mm2) were determined by ultrasonography. Associations between B-Pb and the different outcomes were analysed using Poisson and linear regression models, adjusted for potential confounders. RESULTS: Atherosclerotic plaque was present in 57% of the individuals, for whom the median total plaque area was 16 mm2 (range: 0.2-222). The median B-Pb concentration was 14 µg/L (range: 0.75-203). After adjusting for potential confounders, individuals in the fourth quartile of B-Pb (Q4) had a prevalence ratio (PR) for plaque of 1.08 (95% CI: 1.01, 1.16) when compared with the first quartile (Q1). A 10 µg/L increase in B-Pb concentrations was associated with an increase of 0.92 mm2 (95% CI: 0.14, 1.71) in total plaque area. The PR for large plaque was 1.09 (95% CI: 0.84, 1.42 for Q4 vs Q1). CONCLUSIONS: This study shows an association between B-Pb and atherosclerosis in the carotid arteries providing some support for the hypothesis that atherosclerosis is one of the mechanisms underlying the association between lead exposure and cardiovascular disease.

Urinary iodine excretion and optimal time point for sampling when estimating 24-h urinary iodine.

Iodine deficiency may cause thyroid dysfunction. The iodine intake in a population is measured by urinary iodine concentration (UIC) in spot samples or 24-h urinary iodine excretion (24UIE). 24UIE is considered the gold standard and may be estimated using an equation including UIC, urinary creatinine concentration, sex and age (e24UIE). The aims of this study were to evaluate the preferable timing of UIC when using this equation and assess the variability of UIE. Sixty healthy non-smoking women (n 31) and men (n 29) were included in Gothenburg, Sweden. Twelve urine samples were collected at six fixed times on two separate days. Variability was calculated for UIC, 24UIE, e24UIE, iodine excretion per hour (iHr) and UIC adjusted for creatinine and specific gravity. Median 24UIE was 156 µg/24 h and the median UIC (all spot samples) was 104 µg/l. UIC (P < 0·001), 24UIE (P = 0·001) and e24UIE (P < 0·001) were significantly higher in men. e24UIE was relatively similar to 24UIE. However, when e24UIE was calculated from UIC in the first void, it was about 15 % lower than 24UIE (P < 0·001). iHr was lowest in the morning and highest in the afternoon. Median iHr was higher in men (7·4 v. 5·3 µg/h, P < 0·001). The variability of UIE was higher within individuals than between individuals. This study suggests that most time points for estimation of individual 24UIE are appropriate, but they should preferably not be collected in the first void.

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.

Low-level exposure to lead, cadmium and mercury, and histopathological findings in kidney biopsies.

BACKGROUND: Lead (Pb), cadmium (Cd) and mercury (Hg) are all nephrotoxic metals, and a large part of the body burden of Cd and Hg is found in the kidneys. There are, however, few studies on associations between exposure to these toxic metals and renal biopsy findings, and none at low-level exposure. AIM: To examine the hypothesis that low-level concentration of Pb, Cd or Hg in the kidneys is associated with histopathological changes in the kidneys. METHODS: We determined concentrations of Pb, Cd and Hg in kidney, blood and urine in 109 healthy kidney donors, aged 24-70 years. The renal biopsies were scored according to the Banff classification regarding tubular atrophy, interstitial fibrosis, glomerulosclerosis, arteriosclerosis, and arteriolohyalinosis. Kidney function was assessed based on glomerular filtration rate (GFR) as well as urinary excretion of albumin, low molecular weight proteins, kidney injury molecule 1 and N-acetylglucose aminidase. Associations between metal concentrations and histopathological changes, were assessed in models also including age, sex and smoking. RESULTS: The median kidney concentrations of Pb, Cd and Hg were 0.08, 13 and 0.21 µg/g, respectively. There were signs of tubular atrophy in 63%, interstitial fibrosis in 21%, glomerulosclerosis in 71%, arteriosclerosis in 47%, and arteriolohyalinosis in 36% of the donors, but, as could be expected, the histopathological findings were limited, mostly Banff grade 1. In models adjusted for age, sex and smoking, kidney Cd was positively associated with tubular atrophy (p = 0.03) and possibly with arteriolohyalinosis (p = 0.06). Kidney Hg was associated with arteriosclerosis (p = 0.004). DISCUSSION AND CONCLUSIONS: The results suggest that even low levels of Cd in the kidney can induce a mild degree of tubular atrophy. This is in line with previous findings at high-level Cd exposure. The association between kidney Hg and renal arteriosclerosis was unexpected, and may be a chance finding.

Variability of lead in urine and blood in healthy individuals.

BACKGROUND: Lead is a non-essential toxic trace element. Lead in blood (BPb) is the most common biomarker of lead exposure but lead in urine (UPb) has also been used. There is, however, limited data on the variability of UPb in the general population and the association with BPb. OBJECTIVES: Our aims were to assess variability of lead in repeated blood and urine samples. The diurnal variation of UPb was also examined as well as associations with BPb. METHODS: We established an openly available biobank including 60 healthy non-smoking individuals, 29 men and 31 women, 21-64 years of age (median 31 years), with repeated sampling of blood and urine. Timed urine samples were collected at six fixed time points in two 24 h periods, about one week apart, and adjusted for creatinine and specific gravity (SG). BPb and UPb were analyzed by inductively coupled plasma mass spectrometry. The within- and between-individual variabilities and intra-class correlation coefficients (ICCs; ratios of the between-individual to total observed variances) were calculated using mixed-effects models. RESULTS: The ICCs for UPb samples were mostly above 0.5, when adjusted for creatinine or SG, and higher for overnight samples compared with daytime samples. The highest ICCs were obtained for BPb (ICC = 0.97) and for urine samples corrected for dilution by SG or creatinine. The ICC was 0.66 for overnight samples adjusted for creatinine. High correlations with BPb were found for 24 h UPb (rs = 0.77) and overnight samples, e.g. rs = 0.74 when adjusted for SG. There was diurnal variation of UPb with lowest excretion rate in overnight samples. There was also a significant association between the Pb excretion rate and urinary flow rate. CONCLUSIONS: In addition to BPb, UPb adjusted for creatinine or SG seems to be a useful biomarker for exposure assessment in epidemiological studies.

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.

Occupational exposure to soft paper dust and mortality.

OBJECTIVES: Occupational exposure to soft paper dust is associated with impaired lung function. Whether there is an increased risk for asthma or chronic obstructive pulmonary disease (COPD) is unclear. METHODS: We studied 7870 workers from three Swedish soft paper mills, and defined high-exposed workers, as having been exposed to soft paper dust exceeding 5 mg/m3 for at least 5 years. The remaining workers were classified as 'low exposed'. Person-years at risk were calculated and stratified according to gender, age and calendar-year. The follow-up time was from 1960 to 2013. The expected numbers of deaths were calculated using the Swedish population as reference and standardised mortality ratios (SMRs) with 95% CIs were assessed. RESULTS: There was an increased mortality due to obstructive lung disease (asthma and COPD), among high-exposed workers, SMR 1.89, 95% CI 1.20 to 2.83, based on 23 observed cases. High-exposed workers had an increased mortality from asthma, SMR 4.13, 95% CI 1.78 to 8.14, based on eight observed cases. The increased asthma mortality was also observed among high-exposed men, SMR 4.38, 95% CI 1.42 to 10.2, based on five observed cases. The asthma mortality among low-exposed workers, both men and women, was not increased. The COPD mortality was not clearly increased among high-exposed workers (SMR 1.52, 95% CI 0.85 to 2.50). CONCLUSION: High occupational exposure to soft paper dust increases the mortality due to asthma, and the results suggest that soft paper dust levels in workplaces should be below 5 mg/m3.

Lung function and paper dust exposure among workers in a soft tissue paper mill.

PURPOSE: To study respiratory effects of exposure to soft paper dust exposure, a relationship that is rarely studied. METHODS: Soft tissue paper mill workers at a Swedish paper mill were investigated using a questionnaire and lung function and atopy screening. Spirometry without bronchodilation was performed with a dry wedge spirometer, and forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were obtained and expressed as percent predicted. Exposure to soft paper dust was assessed from historical stationary and personal measurements of total dust, in addition to historical information about the work, department, and production. The impact of high exposure to soft paper dust (> 5 mg/m3) vs. lower exposure ≤ 5 mg/m3, as well as cumulative exposure, was analyzed using multiple linear regression models. Multivariate models were adjusted for smoking, atopy, gender, and body mass index. RESULTS: One hundred ninety-eight current workers (124 male and 74 female) were included. There were significant associations between both cumulative exposure and years of high exposure to soft paper dust and impaired lung function. Each year of high exposure to soft paper dust was associated with a 0.87% decrease in FEV1 [95% confidence interval (CI) - 1.39 to - 0.35] and decreased FVC (- 0.54%, 95% CI - 1.00 to - 0.08) compared to the lower exposed workers. CONCLUSIONS: The present study shows that occupational exposure to soft paper dust (years exceeding 5 mg/m3 total dust) is associated with lung function impairment and increased prevalence of obstructive lung function impairment.

A semi-quantitative job exposure matrix for dust exposures in Swedish soft tissue paper mills.

BACKGROUND: Total paper dust exposure has been associated with respiratory problems among workers in the soft tissue paper industry. However, a comprehensive job exposure matrix (JEM) has not been developed for application to this industry. Our study was intended to address this need and to support further studies of mortality and morbidity in a cohort of Swedish workers from this industry. METHODS: We evaluated four participating soft tissue paper mills in Sweden. We combined information on process and equipment status from the mills with knowledge of the mills obtained through research efforts and paper dust measurements made at all four mills to develop a semi-quantitative JEM with seven dust exposure levels. The JEM was targeted at workers enrolled into a soft tissue paper mill cohort and working any time between 1960 and 2009. RESULTS: The JEM includes a total of 14 421 cells, with each cell corresponding to the exposure for a job title, department, or work location for a one-year period. Exposure levels in the JEM were estimated to decline at three of the four mills from 1971 to 2009, but overexposures (ie, exceedances of the relevant occupational exposure limits) remained common at the end of the period. CONCLUSIONS: The JEM results highlight the need for ongoing exposure control efforts in the soft tissue paper industry, and will inform ongoing epidemiological studies of the health effects of exposure to paper dust in Sweden. It is freely available for use by other researchers.

Biomarkers of blood cadmium and incidence of cardiovascular events in non-smokers: results from a population-based proteomics study.

BACKGROUND: Cadmium is a toxic metal with multiple adverse health effects, including risk of cardiovascular disease (CVD). The mechanistic link between cadmium and CVD is unclear. Our aim was to examine the associations between blood cadmium (B-Cd) and 88 potential protein biomarkers of CVD. METHODS: B-Cd and 88 plasma proteins were measured in a community-based prospective cohort, the Malmö Diet and Cancer study. The primary analysis was performed in never smokers (n = 1725). Multiple linear regression was used with adjustments for age and sex, and correction for multiple comparisons using the false discovery rate method. Proteins significantly associated with B-Cd were replicated in long-term former smokers (n = 782). Significant proteins were then studied in relation to incidence of CVD (i.e., coronary events or ischemic stroke) in never smokers. RESULTS: Fifteen proteins were associated with B-Cd in never smokers. Eight of them were replicated in long-term former smokers. Kidney injury molecule-1, fibroblast growth factor-23 (FGF23), tumor necrosis factor receptor-2, matrix metalloproteinase-12, cathepsin L1, urokinase plasminogen activator receptor, C-C motif chemokine-3 (CCL3), and chemokine (C-X3-C motif) ligand-1 were associated with B-Cd both in never smokers and long-term former smokers. Except for CCL3 and FGF23, these proteins were also significantly associated with incidence of CVD. CONCLUSIONS: B-Cd in non-smokers was associated with eight potential plasma biomarkers of CVD and kidney injury. The results suggest pathways for the associations between B-Cd and CVD and kidney injury.

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.

Blood Lead Levels and Decreased Kidney Function in a Population-Based Cohort.

BACKGROUND: Environmental lead exposure has been associated with decreased kidney function, but evidence from large prospective cohort studies examining low exposure levels is scarce. We assessed the association of low levels of lead exposure with kidney function and kidney disease. STUDY DESIGN: Prospective population-based cohort. SETTING & PARTICIPANTS: 4,341 individuals aged 46 to 67 years enrolled into the Malmö Diet and Cancer Study-Cardiovascular Cohort (1991-1994) and 2,567 individuals subsequently followed up (2007-2012). PREDICTOR: Blood lead concentrations in quartiles (Q1-Q4) at baseline. OUTCOMES: Change in estimated glomerular filtration rate (eGFR) between the baseline and follow-up visit based on serum creatinine level alone or in combination with cystatin C level. Chronic kidney disease (CKD) incidence (185 cases) through 2013 detected using a national registry. MEASUREMENTS: Multivariable-adjusted linear regression models to assess associations between lead levels and eGFRs at baseline and follow-up and change in eGFRs over time. Cox regression was used to examine associations between lead levels and CKD incidence. Validation of 100 randomly selected CKD cases showed very good agreement between registry data and medical records and laboratory data. RESULTS: At baseline, 60% of study participants were women, mean age was 57 years, and median lead level was 25 (range, 1.5-258) µg/L. After a mean of 16 years of follow-up, eGFR decreased on average by 6mL/min/1.73m2 (based on creatinine) and 24mL/min/1.73m2 (based on a combined creatinine and cystatin C equation). eGFR change was higher in Q3 and Q4 of blood lead levels compared with Q1 (P for trend = 0.001). The HR for incident CKD in Q4 was 1.49 (95% CI, 1.07-2.08) compared with Q1 to Q3 combined. LIMITATIONS: Lead level measured only at baseline, moderate number of CKD cases, potential unmeasured confounding. CONCLUSIONS: Low-level lead exposure was associated with decreased kidney function and incident CKD. Our findings suggest lead nephrotoxicity even at low levels of exposure.

Relationship between mercury in kidney, blood, and urine in environmentally exposed individuals, and implications for biomonitoring.

BACKGROUND: Individuals without occupational exposure are exposed to mercury (Hg) from diet and dental amalgam. The kidney is a critical organ, but there is limited information regarding the relationship between Hg in kidney (K-Hg), urine (U-Hg), blood (B-Hg), and plasma (P-Hg). OBJECTIVES: The aim was to determine the relationship between K-Hg, U-Hg, B-Hg, and P-Hg among environmentally exposed individuals, estimate the biological half-time of K-Hg, and provide information useful for biomonitoring of Hg. METHODS: Kidney cortex biopsies and urine and blood samples were collected from 109 living kidney donors. Total Hg concentrations were determined and the relationships between K-Hg, U-Hg, P-Hg, and B-Hg were investigated in regression models. The half-time of K-Hg was estimated from the elimination constant. RESULTS: There were strong associations between K-Hg and all measures of U-Hg and P-Hg (rp=0.65-0.84, p<0.001), while the association with B-Hg was weaker (rp=0.29, p=0.002). Mean ratios between K-Hg (in µg/g) and U-Hg/24h (in µg) and B-Hg (in µg/L) were 0.22 and 0.19 respectively. Estimates of the biological half-time varied between 30 and 92days, with significantly slower elimination in women. Adjusting overnight urine samples for dilution using urinary creatinine resulted in less bias in relation to K-Hg or U-Hg/24h, compared with other adjustment techniques. CONCLUSIONS: The relationship between K-Hg and U-Hg is approximately linear. K-Hg can be estimated using U-Hg and gender. Women have longer half-time of Hg in kidney compared to men. Adjusting overnight urine samples for creatinine concentration resulted in less bias.

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.

Cadmium exposure is associated with soluble urokinase plasminogen activator receptor, a circulating marker of inflammation and future cardiovascular disease.

BACKGROUND: Diet and smoking are the main sources of cadmium exposure in the general population. Cadmium increases the risk of cardiovascular diseases, and experimental studies show that it induces inflammation. Blood cadmium levels are associated with macrophages in human atherosclerotic plaques. Soluble urokinase-type plasminogen activator receptor (suPAR) is an emerging biomarker for cardiovascular events related to inflammation and atherosclerotic plaques. The aim was to examine whether blood cadmium levels are associated with circulating suPAR and other markers of inflammation. METHODS: A population sample of 4648 Swedish middle-aged women and men was examined cross-sectionally in 1991-1994. Plasma suPAR was assessed by ELISA, leukocytes were measured by standard methods, and blood cadmium was analysed by inductively coupled plasma mass spectrometry. Prevalent cardiovascular disease, ultrasound-assessed carotid plaque occurrence, and several possible confounding factors were recorded. RESULTS: After full adjustment for risk factors and confounding variables, a 3-fold increase in blood cadmium was associated with an 10.9% increase in suPAR concentration (p<0.001). In never-smokers, a 3-fold increase in blood cadmium was associated with a 3.7% increase in suPAR concentration (p<0.01) after full adjustment. Blood cadmium was not associated with C-reactive protein, white blood cell count and Lp-PLA2 but with neutrophil/lymphocyte ratio in one of two statistical models. CONCLUSIONS: Exposure to cadmium was associated with increased plasma suPAR in the general population, independently of smoking and cardiovascular disease. These results imply that cadmium is a possible cause for raised levels of this inflammatory marker.

Low-level exposure to lead, blood pressure, and hypertension in a population-based cohort.

BACKGROUND: Environmental lead exposure is a possible causative factor for increased blood pressure and hypertension, but large studies at low-level exposure are scarce, and results inconsistent. OBJECTIVE: We aimed to examine the effects of environmental exposure to lead in a large population-based sample. METHODS: We assessed associations between blood lead and systolic/diastolic blood pressure and hypertension in 4452 individuals (46-67 years) living in Malmö, Sweden, in 1991-1994. Blood pressure was measured using a mercury sphygmomanometer after 10min supine rest. Hypertension was defined as high systolic (≥140mmHg) or diastolic (≥90mmHg) blood pressure and/or current use of antihypertensive medication. Blood lead was calculated from lead in erythrocytes and haematocrit. Multivariable associations between blood lead and blood pressure or hypertension were assessed by linear and logistic regression. Two-thirds of the cohort was re-examined 16 years later. RESULTS: At baseline, mean blood pressure was 141/87mmHg, 16% used antihypertensive medication, 63% had hypertension, and mean blood lead was 28µg/L. Blood lead in the fourth quartile was associated with significantly higher systolic and diastolic blood pressure (point estimates: 1-2mmHg) and increased prevalence of hypertension (odds ratio: 1.3, 95% confidence interval: 1.1-1.5) versus the other quartiles after adjustment for sex, age, smoking, alcohol, waist circumference, and education. Associations were also significant with blood lead as a continuous variable. Blood lead at baseline, having a half-life of about one month, was not associated with antihypertensive treatment at the 16-year follow-up. CONCLUSIONS: Low-level lead exposure increases blood pressure and may increase the risk of hypertension.

Health impacts of anthropogenic biomass burning in the developed world.

Climate change policies have stimulated a shift towards renewable energy sources such as biomass. The economic crisis of 2008 has also increased the practice of household biomass burning as it is often cheaper than using oil, gas or electricity for heating. As a result, household biomass combustion is becoming an important source of air pollutants in the European Union.This position paper discusses the contribution of biomass combustion to pollution levels in Europe, and the emerging evidence on the adverse health effects of biomass combustion products.Epidemiological studies in the developed world have documented associations between indoor and outdoor exposure to biomass combustion products and a range of adverse health effects. A conservative estimate of the current contribution of biomass smoke to premature mortality in Europe amounts to at least 40 000 deaths per year.We conclude that emissions from current biomass combustion products negatively affect respiratory and, possibly, cardiovascular health in Europe. Biomass combustion emissions, in contrast to emissions from most other sources of air pollution, are increasing. More needs to be done to further document the health effects of biomass combustion in Europe, and to reduce emissions of harmful biomass combustion products to protect public health.

Cadmium exposure and atherosclerotic carotid plaques--results from the Malmö diet and Cancer study.

BACKGROUND: Epidemiological studies indicate that cadmium exposure through diet and smoking is associated with increased risk of cardiovascular disease. There are few data on the relationship between cadmium and plaques, the hallmark of underlying atherosclerotic disease. OBJECTIVES: To examine the association between exposure to cadmium and the prevalence and size of atherosclerotic plaques in the carotid artery. METHODS: A population sample of 4639 Swedish middle-aged women and men was examined in 1991-1994. Carotid plaque was determined by B-mode ultrasound. Cadmium in blood was analyzed by inductively coupled plasma mass spectrometry. RESULTS: Comparing quartile 4 with quartile 1 of blood cadmium, the odds ratio (OR) for prevalence of any plaque was 1.9 (95% confidence interval 1.6-2.2) after adjustment for sex and, age; 1.4 (1.1-1.8) after additional adjustment for smoking status; 1.4 (1.1-1.7) after the addition of education level and life style factors; 1.3 (1.03-1.8) after additional adjustment for risk factors and predictors of cardiovascular disease. No effect modification by sex was found in the cadmium-related prevalence of plaques. Similarly, ORs for the prevalence of small and large plaques were after full adjustment 1.4 (1.0-2.1) and 1.4 (0.9-2.0), respectively. The subgroup of never smokers showed no association between cadmium and atherosclerotic plaques. CONCLUSIONS: These results extend previous studies on cadmium exposure and clinical cardiovascular events by adding data on the association between cadmium and underlying atherosclerosis in humans. The role of smoking remains unclear. It may both cause residual confounding and be a source of pro-atherogenic cadmium exposure.

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.