AIR POLLUTION AND INFLAMMATORY RESPONSE IN MYOCARDIAL INFARCTION SURVIVORS: GENE-ENVIRONMENT INTERACTION IN A HIGH RISK GROUP (AIRGENE) Epidemiological research during the last decade has indicated that exposure to air pollution at the levels presently measured in Europe is associated with an increase in respiratory and cardiovascular morbidity and mortality. Particulate matter (PM) appears to be the air pollutant most consistently associated with adverse health outcomes. Although the toxicological mechanism has not yet been established, the small size fraction of ambient aerosols, measured as PM 10 (particles with an aerodynamic diameter less than 10μm) or PM 2.5 (less than 2.5μm), rather than the larger particles is considered to be responsible for most of the health effects. The number of concentrations of ultrafine particles (0.01 to 0.1μm) is hypothesised to be of particular concern. The study has the objectives To assess inflammatory responses in association with ambient air pollution concentrations in myocardial infarction (MI) survivors in six European cities. To define susceptible subgroups of myocardial infarction survivors based on genotyping Introduction Study setting Germany: Peters A. (coordinator), Brueske-Hohlfeld I., Cyrys J., Henneberger A., Ibald-Mulli A., Illig T., Kirchmair H., Kolz M., Loewel H., Meisinger C., Rueckerl R., Schaffrath Rosario A, Wichmann HE., Koenig W., Italy: Forastiere F. (PI), Picciotto S., Perucci C., Pistelli R., Santarelli P., Finland: Pekkanen J. (PI), Lanki T., Tiittanen P., Salomaa V., Eriksson J., Kulmala M.(PI), Aalto P. Paatero P., Sweden: Bellander T. (PI), Nyberg F., Berglind N., Pershagen G., Spain: Sunyer J.(PI), Marrugat J., Jacquemin B., Greece: Katsouyanni K.(PI), Chrysohoou C., Panagiotakos D., Antoniades C. To provide evidence based information that will facilitate the development of appropriate public health strategies relevant for European initiatives to reduce the negative effects of ultrafine particles and traditional air pollutants on the exacerbation of cardiovascular disease and to release guidelines for high-risk populations. In particular we plan to address the questions about dose-response relationships between air pollutants and biomarkers of systemic inflammation in survivors of myocardial infarction which size of fine particle mass is most relevant (Ultrafine, PM 2.5 or PM 10 ). which subgroups are especially susceptible to the effects of particulate air pollution due to their genetic predisposition In the light of recent provocative results on the role of traffic exposure and MI onset (Peters et al. NEJM, 2004) the study might be of importance for regulatory decisions with respect to establishing PM 2.5 and other pollutant standards in Europe. Application of Results AIRGENE STUDY GROUP AIRGENE Study areas: Athens, Greece Augsburg, Germany Barcelona, Spain Helsinki, Finland Rome, Italy Stockholm, Sweden Centre# Baseline visits # Blood samples (baseline and follow up) Study period Athens Augsburg Barcelona Helsinki Rome Stockholm Total Six examinations per participant Baseline visit: questionnaires on demographic information, living conditions and disease history and ECG recording Follow-up examinations: short questionnaire on acute events and blood withdrawal to determine inflammatory markers and single nucleotide polymorphisms Health outcomes Study population Air pollution Ultrafine particle concentrations will be measured at a central site in each city traditional air pollution concentrations will be obtained from the local air hygiene networks. Statistical analyses Time-series methods with gene-environment interactions for subgroups In total 95.2% of targeted 1200 subjects were recruited and 87.6% of targeted blood samples were obtained. Measurements