A commonly-assumed paradigm holds that the primary genetic determinant of 
cardiovascular disease resides within the DNA sequence of our genes. This 
paradigm can be challenged. For example, how do sequence changes in the 
non-coding region of the genome influence phenotype? Why are all diseases not 
shared between identical twins? Part of the answer lies in the fact that the 
environment or exogenous stimuli clearly influence disease susceptibility, but 
it was unclear in the past how these effects were signalled to the static DNA 
code. Epigenetics is providing a newer perspective on these issues. Epigenetics 
refers to chromatin-based mechanisms important in the regulation of gene 
expression that do not involve changes to the DNA sequence per se. The field can 
be broadly categorized into three areas: DNA base modifications (including 
cytosine methylation and cytosine hydroxymethylation), post-translational 
modifications of histone proteins, and RNA-based mechanisms that operate in the 
nucleus. Cardiovascular disease pathways are now being approached from the 
epigenetic perspective, including those associated with atherosclerosis, 
angiogenesis, ischemia-reperfusion damage, and the cardiovascular response to 
hypoxia and shear stress, among many others. With increasing interest and 
expanding partnerships in the field, we can expect new insights to emerge from 
epigenetic perspectives of cardiovascular health. This paper reviews the 
principles governing epigenetic regulation, discusses their presently-understood 
importance in cardiovascular disease, and considers the growing significance we 
are likely to attribute to epigenetic contributions in the future, as they 
provide new mechanistic insights and a host of novel clinical applications.