Genetic and epigenetic factors are of great importance in cardiovascular biology 
and disease. Tobacco-smoking, one of the most important cardiovascular risk 
factors, is itself partially determined by genetic background and is associated 
with altered epigenetic patterns. This could render the genetics and epigenetics 
of smoking-related cardiovascular disease a textbook example of environmental 
epigenetics and modern approaches to multimodal data analysis. A pronounced 
association of smoking-related methylation patterns in the F2RL3 gene with 
prognosis in patients with stable coronary heart disease has recently been 
described. Nonetheless, surprisingly little concrete knowledge on the role of 
specific genetic variants and epigenetic modifications in the development of 
cardiovascular diseases in people who smoke has been accumulated. Beyond the 
current knowledge, the present review briefly outlines some chief challenges and 
priorities for moving forward in this field.