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"Air pollution and inflammatory response in myocardial infarction survivors: gene-environment interaction in a high risk group" (2003 - ongoing)

(also availble as pdf-file [110 KB] or Powerpoint-file [1 MB])

Main study objective:
The initial objective of the study was to assess the inflammatory response in association with ambient concentrations of air pollution in myocardial infarction survivors in 6 European cities and to define susceptible subgroups of myocardial infarction survivors based on genotyping.
Ongoing analyses are based on further genotyping and follow-up of the study participants.

Specific aims:

  • To compare the inflammatory response of ultrafine particles to the response of traditional air pollutants.
  • To provide insight into the mechanisms leading from exposure to ambient air pollution to early biological effects in high-risk populations.
  • To determine the role of the variation in genes of inflammatory responses by assessing the gene-environment interactions for air pollution exposures.
  • To provide insight into the mechanisms leading from exposure to ambient air pollution to early biological effects in high-risk populations.

Study design:

Prospective panel study with repeated clinical examinations.

Study population:

Center#Baseline visits:#Blood samples
(baseline and follow up)
Study period
Athens    108    486    15.09.03-30.07.04
Augsburg    200    1.14419.05.03-23.02.04
Barcelona    169    1.119    03.09.03-16.06.04
Helsinki    195    1.155    10.09.03-04.06.04
Rome    134    741    25.09.03-14.07.04

Study areas:
Athens, Greece; Augsburg, Germany; Barcelona, Spain; Helsinki, Finland; Rome, Italy; Stockholm, Sweden       

Study methods:
Health assessment:
Each subject was followed over a period of 6 months. Clinical examinations included

  • a baseline examination with ECG-recording (to characterise the degree of heart disease), blood sampling (to determine e.g. inflammatory markers, BNP (B-type natriuretic peptide) and DNA extraction for the determination of DNA variants, blood pressure measurements, anthropometric measurements and questionnaire,
  • a total of 5 follow-up examinations (every four to five weeks) with blood sampling for the determination of inflammatory markers,
  • information on respiratory and cardiovascular symptoms as well as eating habits collected through a questionnaire at each clinical visit,
  • diary information on respiratory and cardiovascular symptoms as well as medication use throughout the study period.

Assessment of ambient air pollution:
Ultrafine particle concentrations were measured at a central site in each city and traditional air pollution concentrations were obtained from the local air hygiene networks.

Study period:   
Field phase: May 2003 - July 2004
Data management: May 2003 - August 2005
Data analyses: from September 2004
Funding: January 2003 - June 2006

Current status:
Analyses ongoing

Helmholtz Zentrum München - Institute of Epidemiology II, Neuherberg (Germany):
Annette Peters (PI), Irene Brueske (consultant), Josef Cyrys (air pollution measurement), Uta Geruschkat (data management), Sonja Greven (data management, statistical analyses) Alexandra Schneider (née Henneberger, data coordination, statistical analyses), Angela Ibald-Mulli (study design, study materials until 2004), Thomas Illig (genetical consultant), Hanna Kirchmair (technical assistant), Melanie Waldenberger (née Kolz, genetical analyses, statistical analyses), Mainsi Marowsky-Köppl (data management), Regina Pickford (née Rückerl, quality assurance, statistical analyses), Angelika Schaffrath Rosario (data coordination until 2004), H.-Erich Wichmann (consultant.

in cooperation with

KORA Herzinfarktregister, Zentralklinikum Augsburg (Germany)
Hannelore Löwel


KORA – Studienzentrum Augsburg (Germany): Christa Meisinger


Partner II - Ulm, Germany:

  • University of Ulm – Abteilung für Innere Medizin II, Ulm
    Wolfgang Koenig

Partner III - Italy:

  • Rome E Health Authority, Department of Epidemiology, Rome
    Francesco Forastiere, Carlo Perucci, Sally Picciotto

in cooperation with

  • Department of Clinical Medicine, Catholic University, Rome
    Riccardo Pistelli, Fiammetta Baldari


  • Department of Cardiology, Catholic University, Rome
    Pietro Santarelli

Partner IV - Finland:

  • Department of Environmental Health, National Public Health Institute (KTL), Kuopio,
    Juha Pekkanen, Timo Lanki, Pekka Tiittanen
  • Department of Epidemiology and Health Promotion, National Public Health Institute (KTL), Helsinki,  
    Veikko Salomaa, Johan Eriksson
  • Helsinki University Hospital, Helsinki,
    Kari Luotola

Partner V - Sweden:

  • Division of Environmental Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm
    Tom Bellander, Niklas Berglind, Fredrik Nyberg, Goran Pershagen

in cooperation with

  • Unit of Environmental Health, Department of Occupational and Environmental Health, Stockholm County Council, Stockholm,
    Tom Bellander, Niklas Berglind


Partner VI - Spain:

  • IMIM – Institut Municipal d’Investigació Mèdica, Barcelona,
    Jordi Sunyer, Jaume Marrugat, Bénédicte Jacquemin

Partner VII - Greece:

  • Department of Hygiene and Epidemiology University of Athens Medical School, Athens
    Klea Katsouyanni, Demosthenes Panagiotakos
  • University of Athens, Medical School, Dept of Cardiology, Athens
    Christina Chrysohoou, John Mitropoulos, Charalambos Antoniades, Konstantina Kosma, Christis Pitsavos

Partner VIII - Finland II:

  • UH – University of Helsinki Department of Physical Sciences (UHEL), University of Helsinki,
    Markku Kulmala, Pasi Aalto, Pentti Paatero

EU Contract Number: QLK4-CT-2002-O2236 2003-2005

Related publications:

  • Brüske I, Hampel R, Baumgärtner Z, Rückerl R, Greven S, Koenig W, Peters A. Schneider A. 2011. Ambient Air pollution and lipoprotein-associated phospholipase A2 in myocardial infarction survivors. Environ Health Perspect 119(7):921-6.

  • Kraus U, Breitner S, Schnelle-Kreis J, Cyrys J, Lanki T, Rückerl R, Schneider A, Brüske-Hohlfeld I, Devlin R, Wichmann HE, Zimmermann R, Peters A. 2011. Particulate Air Pollution and Cardiovascular Symptoms in Myocardial Infarction Survivors: Results on Particle Associated Organic Compounds. Inhalation Toxicology 23(7): 431-47.

  • Hampel R, Schneider A, Brüske I, Zareba W, Cyrys J, Rückerl R, Breitner S, Korb H, Sunyer J, Wichmann HE, Peters A. Altered Cardiac Repolarization in Association with Air Pollution and Air Temperature in Myocardial Infarction Survivors. Environ Health Perspect. (2010)

  • Luotola K, Pietilä A, Alanne M, Lanki T, Loo BM, Jula A, Perola M, Peters A, Zeller T, Blankenberg S, Salomaa V; Health 2000, FINRISK97, and AIRGENE Study Groups:
    Genetic variation of the interleukin-1 family and nongenetic factors determining the interleukin-1 receptor antagonist phenotypes. Metabolism. 2010 Oct;59(10):1520-7.

  • Karakas M, Baumert J, Greven S, Rückerl R, Peters A, Koenig W.:
    Reproducibility in serial C-reactive protein and interleukin-6 measurements in post-myocardial infarction patients: results from the AIRGENE study.
    Clin Chem. 2010 May;56(5):861-4.

  • Sunyer J, Forastiere F, Pekkanen J, Plana E, Kolz M, Pistelli R, Jacquemin B, Brüske-Hohlfeld I, Pitsavos Ch, Bellander T, Koenig W, Peters A; AIRGENE Study Group:
    Interaction between smoking and the interleukin-6 gene affects systemic levels of inflammatory biomarkers. Nicotine Tob Res. 2009 Nov;11(11):1347-53.

  • Luotola K, Pääkkönen R, Alanne M, Lanki T, Moilanen L, Surakka I, Pietilä A, Kähönen M, Nieminen MS, Kesäniemi YA, Peters A, Jula A, Perola M, Salomaa V; Health 2000 AIRGENE Study Groups: Association of variation in the interleukin-1 gene family with diabetes and glucose homeostasis.
    J Clin Endocrinol Metab. 2009 Nov;94(11):4575-83.

  • Ljungman P, Bellander T, Schneider A, Breitner S, Forastiere F, Hampel R, Illig T, Jacquemin B, Katsouyanni K, von Klot S, Koenig W, Lanki T, Nyberg F, Pekkanen J, Pistelli R, Pitsavos C, Rosenqvist M, Sunyer J, Peters A.:
    Modification of the interleukin-6 response to air pollution by interleukin-6 and fibrinogen polymorphisms.
    Environ Health Perspect. 2009 Sep;117(9):1373-9.

  • Panagiotakos DB, Dimakopoulou K, Katsouyanni K, Bellander T, Grau M, Koenig W, Lanki T, Pistelli R, Schneider A, Peters A on behalf of the AIRGENE Study Group.
    Mediterranean diet and inflammatory response in myocardial infarction survivors.
    Int J Epidemiol. 2009 Jun;38(3):856-66

  • Ljungman P, Bellander T, Nyberg F, Lampa E, Jacquemin B, Kolz M, Lanki T, Mitropoulos J, Müller M, Picciotto S, Pistelli R, Rückerl R, Koenig W, Peters A.
    DNA variants, plasma levels and variability of Interleukin-6 in myocardial infarction survivors: Results from the AIRGENE study.
    Thromb Res. 2009 May;124(1):57-64.

  • Peters A, Greven S, Heid IM, Baldari F, Breitner S, Bellander T, Chrysohoou C, Illig T, Jacquemin B, Koenig W, Lanki T, Nyberg F, Pekkanen J, Pistelli R, Rückerl R, Stefanadis C, Schneider A, Sunyer J, Wichmann HE.
    Fibrinogen Genes Modify the Fibrinogen Response to Ambient Particulate Matter.
    Am J Respir Crit Care Med 179: 484-491 (2009)

  • Rückerl R, Peters A, Khuseyinova N, Andreani M, Koenig W, Meisinger C, Dimakopoulou K, Jordi Sunyer, Lanki T, Nyberg F, Schneider A.
    Determinants of the acute phase protein CRP in myocardial infarction survivors: The role of co-morbidities and environmental factors.
    Clinical Chemistry 55(2): 322-335 (2009)

  • Greven S, Crainiceanu CM, Küchenhoff H, Peters A.
    Restricted Likelihood Ratio Testing for Zero Variance Components in Linear Mixed Models.
    J Comput Graph Stat 17(4): 870-891 (2008)

  • Jacquemin B, Antoniades C, Nyberg F, Plana E, Müller M, Greven S, Salomaa V, Sunyer J, Bellander T, Chalamandris AG, Pistelli R, Koenig W, Peters A.
    Common Genetic Polymorphisms and Haplotypes of Fibrinogen Alpha, Beta, and Gamma Chains Affect Fibrinogen Levels and the Response to Proinflammatory Stimulation in Myocardial Infarction Survivors. The AIRGENE Study.
    J Am Coll Cardiol 52, 941-952 (2008)

  • Khuseyinova N, Greven S, Rueckerl R, Trischler G, Loewel H, Peters A, Koenig W.
    Variability of Serial Lipoprotein-Associated Phospholipase A2 Measurements in Post-Myocardial Infarction Patients: Results from the AIRGENE-Study Center Augsburg.
    Clin Chemistry 54(1), 124-130 (2008)

  • Kolz M, Koenig W, Müller M, Andreani M, Greven S, Illig T, Khuseyinova N, Panagiotakos D, Pershagen G, Salomaa V, Sunyer J, Peters A, for the AIRGENE Study Group:
    DNA variants, plasma levels and variability of C-reactive protein in myocardial infarction survivors: results from the AIRGENE study.
    Eur Heart J 29, 1250-1258 (2008)

  • Picciotto S, Forastiere F, Pistelli R, Koenig W, Lanki T, Ljungman P, Pitsavos C, Ruckerl R, Sunyer J, Peters A.
    Determinants of plasma interleukin-6 levels among survivors of myocardial infarction.
    Eur J Card Prev Rehab 15(6): 631-638 (2008)

  • Schneider A, Panagiotakos D, Picciotto S, Katsouyanni K, Löwel H, Jacquemin B, Lanki T, Staffoggia M, Bellander T, Koenig W, Peters A for the AIRGENE Study Group:
    Air Temperature and Inflammatory Responses in Myocardial Infarction Survivors.
    Epidemiology 19(3), 391-400 (2008)

  • Sunyer J, Pistelli R, Plana E, Andreani M, Baldari F, Kolz M, Koenig W, Pekkanen J, Peters A, Forastiere F:
    Systemic inflammation, genetic susceptibility and lung function.
    Eur Resp J 32, 92-97 (2008)

  • Peters A, Schneider A, Greven S, Bellander T; Forastiere F; Ibald-Mulli A; Illig T; Jacquemin B, Katsouyanni K; Koenig W; Lanki T; Pekkanen J; Pershagen G; Picciotto S; Rückerl R; Schaffrath Rosario A; Stefanadis C; Sunyer J:
    Air Pollution and Inflammatory Response in Myocardial Infarction Survivors: Gene-Environment Interactions in a High-Risk Group.
    Inhalation Toxicology 19 (Suppl. 1):161–175 (2007)

  • Rückerl R, Greven S, Ljungman P, Aalto P, Antoniades C, Bellander T, Berglind N, Chrysohoou C, Forastiere F, Jacquemin B, von Klot S, Koenig W, Küchenhoff H, Lanki T, Pekkanen J, Perucci C, Schneider A, Sunyer J and Peters A for the AIRGENE Study Group:
    Air Pollution and Inflammation (Interleukin-6, C-Reactive Protein, Fibrinogen) in Myocardial Infarction Survivors.
    Environ Health Perspect 115:1072–1080 (2007)

  • Kolz M, Koenig W, Müller M, Andreani M, Greven S, Illig T, Khuseyinova N, Panagiotakos D, Pershagen G, Salomaa V, Sunyer J, Peters A for the AIRGENE Study Group:
    DNA variants, plasma levels and variability of C-reactive protein in myocardial infarction survivors: results from the AIRGENE study.
    Eur Heart J. 29(10):1250-8 (2008). Epub 2007 Oct 22

  • Grau M, Guxens M, Subirana I, Fitó M, Covas MI, Jacquemin B, Sunyer J, Lanki T, Picciotto S, Bellander T, Katsouyanni K, Schneider A, Peters A, Marrugat J; AIRGENE Study Group:
    South-to-North gradient in lipid peroxidation in men with stable coronary artery disease in Europe.
    Eur Heart J 28(23):2841-9 (2007)

  • Jacquemin B, Lanki T, Sunyer J, Cabrera L, Querol X, Bellander T, Moreno N, Peters A, Pey J, Pekkanen J: Levels of outdoor PM2.5, absorbance and sulphur as surrogates for personal exposures among post-myocardial infarction patients in Barcelona, Spain
    Atmos Environ Volume 41, Issue 7, March 2007, Pages 1539-1549

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