As many as 60–80% of ischemic stroke events can be attributed to high blood pressure, dyslipidemia, smoking, and diabetes, and also to atrial fibrillation and valvular heart disease (cardiogenic and embolic ischemic stroke) [78]. A review indicated that about 10–20% of atherosclerotic ischemic strokes can prob-ably be attributed to recently established, probprob-ably causal risk factors for ischemic heart disease: raised ApoB/ApoA1 ratio, obesity, physical inactivity, psy-chosocial stress, and low fruit and vegetable intake [79]. However, their causal role remains to be proven.
While the importance of genes predisposing to stroke cannot be denied [80, 81], the contribution of any single gene towards ischemic stroke is likely to be modest and to apply in selected patients only and in combination with environmental factors or via other epistatic (gene–gene or gene–environmental) effects.
Hankey proposed, based on the well-known Brad-ford Hill criteria on causality, a practical way to consider the causal significance of a risk factor for ischemic stroke [79]:
Is there evidence from experiments in humans?
Is the association between exposure to the risk factor and ischemic stroke shown by means of multiple variable regression analysis to be
independent of other risk factors that may interact with the risk factor or be a confounding risk factor?
Is the association strong?
Is the association consistent from study to study?
Is the temporal relation correct (exposure to the risk factor occurred before the stroke)?
Is there a dose–response relation (increasing risk or severity of stroke associated with increasing dose or duration of exposure to the risk factor)?
Is the association biologically plausible?
Is the association epidemiologically plausible?
Is there evidence that reducing exposure to the risk factor (e.g. by randomized controlled trials or large observational prospective studies) leads to a reduction in the risk of stroke?
It needs to be pointed out that certain issues such as smoking and alcohol drinking, and many other diet-ary factors, can never be properly tested in real life using a controlled trial design, and if such experi-ments would appear, they can only be considered as cross-sectional in a particular population. Therefore, it is very important to understand the inferences that can be drawn from various studies. Techniques such as meta-analysis will help, but only if the original studies were done properly and were comparable.
Therefore, resources should not be allocated dis-proportionately to emerging novel risk factors that may account for up to only 20% of all strokes at the expense of researching the determinants of the rela-tively few established causal factors that account for up to 80% of all strokes. The evidence is strong to suggest that the control of the established risk factors for stroke will result in prevention of a very large number of stroke events and premature deaths.
Chapter summary
On a global scale, stroke is the second most frequent cause of mortality worldwide and a leading cause of disability. It is especially prevalent in low- and middle-income countries. The WHO Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) Stroke Study compared the stroke inci-dence (or more precisely attack rate), mortality, and case fatality in 14 populations aged 35–64 years in the 1980–1990s. The study confirmed the large geo-graphical variation in stroke incidence and mortality, and also in case fatality. More recently, a few coun-tries have systematically collected population-based incidence data for stroke. The relative frequency of different subtypes of stroke varies among popula-tions, and in particular among different ethnic groups. This variation may be in part due to genetic differences or due to differences in risk-factor pro-files. In most populations, changes in stroke mortal-ity, whether declining or increasing, have been principally attributable to changes in case fatality rather than changes in event rates. In many epidemi-ological studies strokes have been defined without
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confirmation by neuroimaging. Definitions by clinical means alone can be imprecise and sometimes mis-leading. In general, stroke mortality rates have declined over recent decades. The overall case fatal-ity (the proportion of deaths among all strokes) is roughly 20% within the first month, and subse-quently increases around 5% per year. Large vari-ations occur between countries both in stroke incidence, mortality, and case fatality. Mortality rates were 3.5-fold higher in low-income countries than in middle-income and high-income countries.
Stroke has a multifactorial origin and a plethora of putative and confirmed risk factors have been listed and tested in various types of studies. Well-known modifiable risk factors for stroke are virtually the same as those for cardiovascular disease in gen-eral: hypertension, smoking, dyslipidemia, diabetes, etc. Among non-modifiable risk factors old age, racial or ethnic factors, low birth weight, and genetic sus-ceptibility play a role. In individuals with non-modifiable risk factors prevention focused on the modifiable ones is particularly important. Several prospective studies have shown that up to 70–80%
of stroke events may be preventable, if people
sim-ultaneously adhere to several healthy lifestyle habits.
Stroke risk assessment and prevention rely on risk profiles in a population. The Framingham Stroke Profile is widely used but hitherto has not been validated in many populations, but many other stroke risk scores have been developed in various populations.
A recent review indicated that about 10–20% of atherosclerotic ischemic strokes can probably be attributed to more recently established, probably causal risk factors for ischemic heart disease: raised ApoB/ApoA1 ratio, obesity, physical inactivity, psy-chosocial stress, and low fruit and vegetable intake.
However, their causal role remains to be proven.
While the importance of genes predisposing to stroke cannot be denied, the contribution of any single gene towards ischemic stroke is likely to be modest and apply in selected patients only and in combination with environmental factors or via other epistatic (gene–gene or gene–environmental) effects. The evidence is strong to state that the con-trol of the established risk factors for stroke will result in prevention of a very large number of stroke events and premature deaths.
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