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

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.