he burden of stroke is unquestionable in a myriad of aspects. Multiple stroke risk factors are known, and some of them are considered strong and primary while others are considered uncertain and secondary. Among the latter, there is hyperlipidemia. As the acute stroke treatment is costly, the saying that prevention is better than treatment bears a special meaning here. In this discussion, as prosecutors from our bar we stand to plead, "Cholesterol -guilty for stroke." Several epidemiological

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... dies demonstrated a correlation between increased blood total cholesterol levels and risk of myocardial infarction. 1,2 The association between cholesterol levels and stroke occurrence is debated in the literature. In the Framingham cohort no connection was found between the levels of cholesterol and the incidence of stroke. 1 Nonetheless, in young women, a positive correlation between total cholesterol levels and stroke-related mortality was observed, while in subjects in 6th and 7th decade of age, an inverse correlation between these parameters was found. 3 The combined analysis of cohort trials showed no significant association between the increased level of serum cholesterol and stroke rate, except for patients younger than 45 years. 4 However, this analysis did not stratify into stroke subgroups and thus a positive association with ischemic stroke might be offset by a negative association with hemorrhagic stroke. This was confirmed in a longitudinal study on men screened for multiple risk factors, as a positive correlation between total cholesterol levels and ischemic stroke risk, and a negative association between cholesterol level and occurrence of all hemorrhagic strokes was demonstrated. Serum cholesterol levels under 4.14 mmol/L increased the risk of fatal intracranial hemorrhage while the levels above 7.23 mmol/L increased the risk of death from ischemic stroke. 5 An overview of Asian subjects showed a trend toward increased risk of hemorrhagic stroke and decreased risk of ischemic stroke in subjects with decreased cholesterol level. 6 A positive correlation between very high total cholesterol levels Ͼ8 mmol/L, and the risk of nonhemorrhagic stroke was demonstrated in a prospective community based study. 7 At this point we can state that there is indeed a convincing point for elevated cholesterol levels to be linked with increased risk of ischemic stroke. The reasons for not finding the clear-cut relationship between cholesterol level and stroke occurrence may be multiple. The longitudinal cohort studies were predestined to evaluate the role of cholesterol in coronary atherosclerosis, but not to investigate its role in stroke. Therefore, by selecting middle-aged subjects for cardiac studies, the older subjects, who were more susceptible to cerebral infarction, were undoubtedly lost. Moreover, analysis of the occurrence of stroke subtypes and differentiation between cholesterol components was not done. Additionally, the prophylactic treatment used might also influence the incidence of stroke. While there may be some missing epidemiological evidence for the correlation between hypercholesterolemia and stroke occurrence, should we stop at this point and set our defendant free? With some circumstantial evidence we would like to prove its guilt. The Heart Protection Study tested the effectiveness of simvastatin in patients with coronary disease, other occlusive disease, or diabetes in conjunction with LDL cholesterol levels at least 3.5 mmol/L. 8 A 24% reduction in the rate of all-cause mortality and fatal or nonfatal vascular events between simvastatin and placebo groups was shown. There was a 25% reduction in the all-cause stroke incidence rate and a 30% reduction in the ischemic stroke incidence rate. Transient ischemic attacks were also significantly less frequent in the simvastatin versus placebo group (2% versus 2.4%). In this trial, there was a subgroup of patients with the history of cerebrovascular disease without coronary heart disease. However, there was no stratification for the past medical events, thus yielding the interpretation of the effects of simvastatin in subgroups untrustworthy. In this subgroup, a 21% relative risk reduction of major vascular events was demonstrated. However, no effect of simvastatin on stroke recurrence was observed. A few meta-analyses on lipid-lowering therapy and coronary prevention were published in the past decade. The most recent one included all randomized trials, published between 1966 and 2001, testing statins, resins, fibrates, niacin, surgical interventions, and diet. 9 There were 10 primary and 28