Environmental effects and gene-environment interactions: air pollution and temperature effects on cardiovascular risk factors.

Hampel, Regina (2011): Environmental effects and gene-environment interactions: air pollution and temperature effects on cardiovascular risk factors.. Dissertation, LMU München: Medizinische Fakultät

Abstract

Epidemiological studies have shown that elevated air pollution levels and day-to-day variations in air temperature are associated with increases in cardiovascular events such as arrhythmias, myocardial infarctions, and sudden cardiac death. Precursors of these events might be acute changes in heart rate, a reduced heart rate variability (HRV), and changes in the repolarization of the heart, such as QTc-prolongation as well as changes in T-wave amplitude. Furthermore, elevated levels of blood markers of inflammation and coagulation might also lead to the observed adverse cardiac health outcomes. There is already a large body of literature with regard to air pollution effects on HRV parameters and blood markers but the exact biological pathways are still unclear. Little is known about the association between temperature and HRV as well as blood markers. Moreover, potential mechanisms how air pollutants and temperature affect repolarization have received less attention. Researchers have reported that individuals with genetic predispositions or underlying diseases such as diabetes mellitus type 2 might be more susceptible to air pollution exposure. Therefore, more comprehensive investigations in these groups of individuals are necessary in order to gain a better insight in the biological mechanisms. In the first publication of this thesis, I examined the effects of air temperature on markers of inflammation and coagulation in men with coronary or pulmonary disease. A temperature decrease was associated with changes in several blood biomarkers such as platelet counts, factor VII, fibrinogen, and C-reactive protein. However, the direction and timing of the relationship differed between patients with coronary and pulmonary disease. In a second publication, I observed a prolongation of the QT-interval in association with elevated levels of particulate matter (PM) in myocardial infarction survivors. This association was more pronounced in participants with at least one minor allele of the NFE2L2 single nucleotide polymorphism (SNP) rs2364725 which is believed to be involved in the defense against oxidative stress. Furthermore, I detected immediate T-wave flattening and delayed increases in T-wave amplitude associated with elevated air pollution levels. The association between temperature and the T-wave amplitude was inversely U-shaped with highest values at 5C. In a third study among participants with diabetes or impaired glucose tolerance (IGT), I detected reduced HRV, predominantly the standard deviation of normal-to-normal intervals, in association with increases in PM and ultrafine particles. These effects were more pronounced in participants with IGT. I also observed air pollution effect modifications by SNPs supposed to influence cardiac rhythm. In conclusion, this thesis confirms and extends published results on short-term air pollution effects on intermediate markers of cardiovascular system. Furthermore, it is among the first to examine air temperature effects on blood and ECG parameters. Certain medical conditions as well as certain genetic profiles seem to make some subpopulations more susceptible to environmental stressors. The observed changes in HRV and blood markers might partly explain the reported associations between environmental conditions and cardiovascular events.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: air pollution, air temperature, heart rate variability, repolarization, blood markers
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 15. Dezember 2011
• 1. Bericht­erstatter:in: Peters, Annette