Search

Exposure to silica has been linked to excess risk of lung cancer and nonmalignant respiratory disease mortality. In this study we estimated risk for both these outcomes in relation to occupational silica exposure as well as the reduction in risk that would result from hypothetical interventions on exposure in a cohort of exposed workers. Analyses were carried out using data from an all-male study population consisting of 2,342 California diatomaceous earth workers regularly exposed to crystalline silica and followed between 1942 and 2011. We estimated subdistribution risk for each event under the natural course and interventions of interest using the parametric g-formula to adjust for healthy-worker survivor bias. The risk ratio for lung cancer mortality, comparing an intervention in which a theoretical maximum exposure limit was set at 0.05 mg/m3 (the current US regulatory limit) with the observed exposure concentrations, was 0.86 (95% confidence interval: 0.63, 1.22). The corresponding risk ratio for nonmalignant respiratory disease mortality was 0.69 (95% confidence interval: 0.52, 0.93). Our findings suggest that risks from both outcomes would have been considerably lower if historical silica exposures in this cohort had not exceeded current regulatory limits.

Introduction: Increased levels of interleukin 6 (IL-6), a marker for systemic inflammation, have been associated with cardiovascular morbidity and mortality. Materials and Methods: We investigated the influence of IL6 gene polymorphisms on mean level and variability of plasma IL-6 in a population of myocardial infarction survivors recruited in six European cities as part of the AIRGENE study. DNA from each individual was collected and genotyped for eight functional and tagging single nucleotide polymorphisms (SNPs) in the IL6 gene. Results: We analyzed 946 subjects with 5520 repeated plasma samples for IL-6 levels. For four IL6 SNPs in high linkage disequilibrium, heterozygous and homozygous minor allele genotypes were associated with an increase in mean plasma IL-6 levels. SNP rs1800795 was associated with a 6.3% increase in IL-6 (95% confidence interval [CI] 1.7-11.2%) For these SNPs, we found that genotypes associated with higher IL-6 levels also tended to be associated to higher between-individual variability of IL-6 levels on the log-scale than other genotypes. Variability over time within individuals varied little by genotype. Conclusions: We found four genetic polymorphisms in the IL6 gene associated with mean level and variability of plasma IL-6 between individuals in myocardial infarction survivors. (C) 2008 Elsevier Ltd. All rights reserved.

Background We identify determinants of plasma interleukin-6 (IL-6) levels in a multicenter panel study of myocardial infarction (MI) survivors, using repeated measurements to evaluate both baseline and time-varying factors. Design and methods Survivors of MI (N=1003) recruited in six European cities had repeated measurements (median: 6/patient) of IL-6. At baseline, participants’ behaviour and medical histories were determined by interview, and blood pressure, anthropometry, cholesterol and N-terminal B-type natriuretic peptide (NT-proBNP) were measured. Short-term exposures and medication intake were recorded at each visit. Generalized additive mixed models were used to analyze associations of IL-6 with baseline and time-varying risk factors, taking into account repeated measurements. Results Age, hour of blood withdrawal, body mass index, pack-years of smoking, NT-proBNP, systolic blood pressure, high-density lipoprotein cholesterol, persistent cough/phlegm and statin use were significantly and independently associated with IL-6 after adjustment for city, recurrent MI, baseline alcohol intake, current active smoking, tea consumption and extreme anger or stress. Conclusion Among MI survivors, IL-6 levels are associated with many traditional cardiovascular risk factors. Patients with elevated NT-proBNP, respiratory symptoms or obesity had higher IL-6 concentrations and may potentially be at greater risk for coronary artery disease progression. Eur J Cardiovasc Prev Rehabil 15:631-638 (C) 2008 The European Society of Cardiology

Aims A South-to-North gradient across Europe exists for the incidence of coronary artery disease (CAD) rates. Low-density lipoprotein (LDL) oxidation is a hallmark of atherosclerosis and CAD development. The aim of our study was to determine whether differences exist in the degree of LDL oxidation in stable CAD patients from different regions of Europe. Methods and results A cross-sectional multicentre study included 790 stable CAD male subjects aged 35-79 years (61.4 +/- 9.5) from six European countries in three regions by latitude: Northern (Finland and Sweden), Central (Germany), and Southern (Greece, Spain, and Italy). Plasma oxidized LDL (oxLDL) levels were determined. Alcohol intake and lipid profile were significantly associated with oxLDL. The Italian participants had the highest oxLDL levels. A sensitivity analysis showed the models yielded higher adjusted oxLDL values in Northern (63.8 U/L) than in Central (57.6 U/L) and Southern populations (56.5 U/L), P < 0.001, after excluding Italian subjects. The probability of Southern Europe scoring the lowest oxLDL levels was > 71% in all fitted models. Conclusion Our findings suggest a gradient in LDL oxidation from Southern to Northern Europe that consistently holds for all levels of LDL, except for Italy; this country displays the highest levels in Europe, for unknown reasons.

Ambient air pollution has been associated with an increased risk of hospital admission and mortality in potentially susceptible sub-populations, including myocardial infarction (MI) survivors. The multicenter epidemiological study described in this report was set up to study the role of air pollution in eliciting inflammation in MI survivors in six European cities, Helsinki, Stockholm, Augsburg, Rome, Barcelona, and Athens. Outcomes of interest are plasma concentrations of the proinflammatory cytokine interleukin 6 (IL-6) and the acute-phase proteins C-reactive protein (CRP) and fibrinogen. In addition, the study was designed to assess the role of candidate gene polymorphisms hypothesized to lead to a modification of the short-term effects of ambient air pollution. In total, 1003 MI survivors were recruited and assessed with at least 2 repeated clinic visits without any signs of infections. In total, 5813 blood samples were collected, equivalent to an average of 5.8 repeated clinic visits per subject (97% of the scheduled 6 repeated visits). Subjects across the six cities varied with respect to risk factor profiles. Most of the subjects were nonsmokers, but light smokers were included in Rome, Barcelona, and Athens. Substantial inter- and intraindividual variability was observed for IL-6 and CRP The study will permit assessing the role of cardiovascular disease risk factors, including ambient air pollution and genetic polymorphisms in candidate genes, in determining the inter- and the intraindividual variability in plasma IL-6, CRP, and fibrinogen concentrations in MI survivors.