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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 PM10 (particles with an aerodynamic diameter less than 10μm) or PM2.5 (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

IntroductionIntroduction

Study settingStudy 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, PM2.5 or PM10).

• 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 PM2.5 and other pollutant standards in Europe.

Application of ResultsApplication 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 161 693 15.09.03-30.07.04

Augsburg 211 1.196 19.05.03-23.02.04

Barcelona 187 1.130 03.09.03-16.06.04

Helsinki 212 1.174 10.09.03-04.06.04

Rome 163 938 25.09.03-14.07.04

Stockholm

208 1.181 03.09.03-24.06.03

Total 1.142 6.312 19.05.03-30.07.04

• 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 analysesTime-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.

MeasurementsMeasurements