mechanism-based treatments will depend on future progression in understanding
the molecular background of stroke. It is worthwhile to highlight that even in
studying such a fundamental biological processes such as neuronal cell death, a
personalized approach must be taken into account since it was shown, for example,
that sex differences exist in molecular pathways involved in neuronal death after
experimental stroke,^13 suggesting therefore that the specific neuroprotective agents
should be designed so as to bring the benefit to female and male patients.
2.2 Genetic Predisposition to Stroke
Epidemiological evidence supports a genetic predisposition for stroke and opens up
opportunities for personalized medicine. Moreover, the discoveries of the genes
related to stroke are helping to identify new molecular and cellular pathways
involved in the etiopathogenesis of the disease and are opening new scenarios for
the treatment of stroke, which were unimaginable before.
The search for the molecular, cellular, and genetic mechanisms involved in the
predisposition and pathology of the stroke is complicated by the complexity of the
disease, with different stroke subtypes having different genetic architecture. The
stroke is cerebrovascular disease, with the variants comprising ischemic stroke
(80–85 % of stroke cases) and cerebral hemorrhage (15–20 % of stroke cases).^14
Moreover, both cerebral hemorrhage and ischemic stroke can have different causes.
For example, the most common causes of ischemic stroke are large-artery stenosis,
small-vessel disease, and cardioembolism, with many other rarer causes, like
carotid and vertebral dissection, vasculitis, and single-gene disorders like cerebral
autosomal dominant arteriopathy with subcortical infarcts and leukoencelophaty
(CADASIL). Many other single gene disorders can cause both ischemic and
hemorrhagic stroke, but these monogenic causes of stroke are rare and contribute
little to the overall population risk of stroke. The heterogeneity of stroke, which
actually is considered to be a syndrome and not a single disease, implicates
involvement of different pathological pathways and represents a challenge for
personalized medicine of stroke.
It is interesting that conventional cardiovascular risk factors (which include
hypertension, smoking, diabetes mellitus, hyperlipidemia, and coexistence of car-
diovascular diseases like ischemic heart disease and atrial fibrillation) fail to
account for all stroke risk, as the proportion of unexplained risk has been estimated
to be as high as about 50 %.^15 The traditional approaches have shown the heritability
(^13) Yuan et al. ( 2009 ).
(^14) Markus ( 2012 ).
(^15) Markus ( 2012 ) and Sacco et al. ( 1989 ).
244 M.M. Pejatovic ́and S. Anzic ́